Iain visits a patient at home, who has frequently tried to harm herself in the past, but decide she does not need help at the moment - despite the concerns of her boyfriend. However, while driving back to the hospital, he witnesses her attempting suicide by jumping off a bridge - which in turn, causes a major crash putting several lives in danger - including Sam's.
Ciara comes back into Dylan's life, while the fallout from the crash affects the whole department.
Wanting to keep busy, Alicia arrives back at work in the ED earlier than expected, and Connie gives her the job of medical lead for the day. OAPs Joseph and Reggie decide to sneak out of their care home and make their way to a diner looking forward to a full English breakfast, but just as they arrive, Reggie collapses and an ambulance is called. Louise is ready to give Dylan a piece of her mind about bringing on a CQC investigation, until she learns that he is going to clean out Sam's locker later on.
Tensions run high on the day of Sam's funeral, as a grieving Iain faces his tribunal hearing.
Iain returns to work, but there is a frosty atmosphere between him and Ruby. Whilst on a call Iain comes across an unconscious Base, and when he awakens Base explains he got kicked out the flat as it was Mia's. Elsewhere, David and Ciara fight over Dylan, and Alicia admits to Ethan that she is not ready for a relationship.
Dylan is forced to treat Ciara when she comes into the hospital suffering from abdominal pains. After looking at her symptoms he orders a pregnancy test, which comes back positive. Meanwhile, Iain secures Base a place in rehab, but on the way there, Base disappears, and Duffy makes doctor's appointment and gets Robyn to cover her.
Ruby and Iain are less than pleased to be working a shift together and their day goes from bad to worse when they are pranked by a group of children and have to deal with an emergency labour. Duffy confides in an old flame.
Jacob is shocked to find Omo, his schizophrenic mother, has arrived in the ED along with his son Blake. Elle goes to deal with Omo, who refuses to believe there is anything wrong and resists treatment, thinking that Elle is keeping her there on Jacob's orders. Elsewhere, Gem asks Ruby if she can swap bedrooms and is delighted when she agrees.
Rash reels from his break up with Gem as she refuses to accept his apology, while David reaches desperation point and gets in touch with Zsa Zsa to help in the quest to find Dylan - but events quickly spiral out of control.
Ciara wakes up on the floor surrounded by smashed glass, and Joel insists on taking her to the ED. Once alone, Ciara apologises to Dylan for the awkwardness of the situation, but as she is discharged she collapses and admits it could be her liver. With the nursing team understaffed, Charlie has to call Duffy in - even though she has recently undertaken a night shift.
Base works for Ross in his meth lab to pay off his debts. He collects 16-year-old Harry to work with them, and watches on as Ross physically asserts his authority over the teenager. Duffy wakes up in a hotel room having slept with Bill. Full of guilt, she sends him away and gets ready to leave. On her way out, she hears a call for help and reluctantly treats Naima, who was found passed out in the hotel swimming pool by her fiance.
Determined to learn from medics in other departments, Louise is excited for a shift on the maternity ward. However, student nurse Jade stumbles into work late, and Louise is not impressed by her actions. Meanwhile, Charlie remains suspicious of Duffy, and Iain makes a call to the wellbeing team, finally seeking help about his mental-health struggles.
Dylan puts himself and Ciara in jeopardy when he takes a chance on love, while student nurse Marty arrives at the ED on his first day eager to please. Louise witnesses an elderly man being robbed by a gang of youths on bicycles, but soon learns not to judge a book by its cover. Elsewhere, Iain gets the runaround when asking for help, and Duffy catches Charlie answering her phone.
In the aftermath of the crash, Ciara is desperate to get away, but Dylan is determined to treat those who have been injured - despite receiving a head wound himself. On his return to the hospital, he reflects on his hopes for a future with Ciara in spite of everything that has happened, while at home, Ciara considers her own needs.
After a hard day, Iain seeks comfort in the wrong place. Duffy makes a shocking diagnosis
Bill is admitted to the emergency department suffering from chest pains. Charlie agrees to help him find out if his daughter is still drinking, but ends up discovering his affair with Duffy. A teenager is brought in after having been apprehended by the police, and while Ethan wants to discharge her as soon as possible, Alicia suspects her case may be more complicated. Marty tries to arrange a date with Joshua - but they may end up having some company.
Dylan faces a traumatic Christmas in Resus. Noel is delighted to have met his Christmas fundraising goal, but can't quite decide on a charity to give the money to.
Iain gets beaten up, and Marty chooses his career over friendship with Jade.
Alicia learns to trust her own medical opinion, and after self-diagnosing herself with dementia, Duffy visits a doctor to get checked. Robyn bans Marty from looking after Charlotte after she finds out he gave her a temporary tattoo, Marty and Jade fight over which of them needs to move out, and Iain and Ruby agree to forget about the kiss.
Alicia finds out that she has been offered a place on a coveted paediatric fellowship in Manchester, forcing her to make a decision on her future. Elsewhere, Marty's lies begin to catch up with him, while Elle is disappointed when she has to hand back to reins as clinical lead to a returning Connie.
Iain heads to Base's flat, but when he does not answer the door he becomes concerned and climbs through a window, only to find Base has taken an overdose. Louise goes out of her way for Ernest when he comes to the ED for a once-over, while Gem and Ruby look for somewhere new to live when Alicia's house goes on the market.
Jan learns the truth about her son and forgives Iain, while Ethan begins to move on from Alicia. Louise stands up for Jade and vows to protect her team in the future, Duffy panics when she forgets that she bought Charlie a birthday present, and Iain signs up for his first counselling session.
Ernest arrives for his surgery, only to find it has been cancelled as there are not enough beds. Louise sets to work freeing up a bed for him, but it is soon taken by another more critical patient. Connie is attacked by an unknown assailant on a flight of stairs, while Rash asks Gem to help him decide between paediatrics and cardiology.
Iain reaches out to someone from his past, but he does not get the response he was hoping for. Connie cannot remember the attacker, and is terrified that they could still be out there. Meanwhile, Marty and Jade learn to work together and decide to call a truce, and Louise takes a stand and hands her resignation to Charlie.
Marty plays counsellor for a couple who having problems with their relationship. After a busy and fulfilling day - treating patients including a girl involved in a hit and run accident, and two women who are attacked in a nightclub - Iain feels that his work with Ruby is done. Elsewhere, Dylan sees maggots cleaning a wound and gets an idea, and Ruby moves in with Jade and Marty.
A cyber-attack rocks Holby hospital at the worst possible time. Meanwhile, Ruby learns to trust her instincts as Iain's life hangs in the balance.
The aftermath of Iain's attempted suicide ripples its way through the emergency department. Gemma struggles to come to terms with what has happened, and makes it her mission to piece together why Ian attempted suicide. Meanwhile, wracked with guilt, Ruby goes out of her way for a patient, and Connie tells Elle off for addressing the team about Iain's progress.
Duffy finally lets Charlie in on her big secret and tells him about her Vascular dementia diagnosis. Charlie decides that it may be best to pull her from the night shifts, when symptoms are most likely to appear. Meanwhile, new registrar Archie Hudson is thrown into the deep end on her first day after leaving her hospital induction early, and Connie reluctantly praises Elle's success.
Archie butts heads with charming paediatric locum registrar Will Noble when they meet in the car park. Will reconnects with old university friend Ethan and ingratiates himself with the staff by treating them to coffees and getting to know them. Archie is not fooled by his charm offensive and keeps a close eye on Will. Elsewhere, Jade learns she's passed her exams by the skin of her teeth, and Gem thanks Jan and Ruby for their help.
Charlie snaps under the pressure of keeping Duffy's ill health a secret, and Rash puts aside his dreams of travelling the world to stick by Gem. Connie is shocked when a paramedic is attacked by an unknown assailant. Meanwhile, Dani arranges to meet with Ruby, and secretly activates a tracker on Ruby's phone.
Connie comes face to face with her attacker, and Will goes above and beyond what is expected of him, but his actions only make things worse. Meanwhile, Ruby starts to feel uncomfortable when Dani keeps turning up out of the blue, Jade's nursing registration comes through, and Jan and Ruby discuss Iain's return.
With Gem's help, Rash makes the choice to follow his dream of travelling. Will risks Connie's wrath to help a patient, Charlie realises that he has underestimated Duffy, and Jade is excited to finally be a registered nurse.
Working as a 999 call handler helps Iain learn to open up, though he feels frustrated not to be out in the field.
Iain goes above and beyond on his first day back as a paramedic after his suicide attempt, and Duffy starts to doubt whether she should have been so open about her diagnosis. Meanwhile, Connie offers Will another interview, and Elle is left feeling hurt when Connie doesn't react to her choice to take a new job.
Will and Archie put aside their differences when Toby is rushed into the ED. Will is torn between Toby's wishes and those of his mother, who wants to try every treatment available, feeling it is her responsibility as a parent. Ruby is annoyed when she spots Dani hanging around the ambulance station again, and the team discusses the idea of Duffy and Charlie renewing their vows.