The 15th and final season opens with the staff dealing with the aftermath of the ambulance explosion. Morris and Neela have trouble handling Pratt's injuries, while Abby makes a mistake diagnosing a mother and daughter injured in the blast.
The ER is on guard as Gates marshals the new interns to treat a terrorist, but it's the new doctor (Angela Bassett) and her tough disposition that has everyone on the defensive. Meanwhile, Neela is on a mission to get Dubenko back on the surgery staff.
Abby's length of service at County comes in handy when she stands up for Sam at the nurses' disciplinary board, but it's of little help in dealing with the new chief (Angela Bassett), who disagrees with Abby on how to treat a gunshot victim. Meanwhile, Neela finally learns of Abby's good news, but is hurt that she had to hear it secondhand.
Banfield defends herself against a thief; Dubenko returns to the surgery team after Brenner's successful protests; a gymnast's injuries arouse the suspicions of Banfield and Gates; and Sarah's surprise piercing upsets Gates.
Neela is surprised by a visit from an old friend, and Brenner treats a school-age stabbing victim. Meanwhile, Sam, whose attention is on her upcoming pharmacology exam, doesn't realize Gates feels neglected. Shane West guest stars.
With Pratt gone, Morris takes on the role of mentor to Chaz, but Banfield disapproves of the complicated medical procedures he's teaching him. Meanwhile, Neela feels disrespected by Banfield when dealing with her intern. Courtney B. Vance guest stars.
Dr. Greene (Anthony Edwards) returns in flashbacks as Banfield recalls his heroics in caring for her son years earlier. The memories are triggered by a 3-year-old girl whom Banfield tries to rescue from drowning. Meanwhile, Gates tries to use his influence to help a homeless veteran, and the interns struggle with their ER responsibilities.
Neela's intern bears the brunt of her anger after he involves the surgery department in a lawsuit. Meanwhile, Brenner loses control with a patient and Gates' obsession with a missing war hero frustrates Sam.
A snowstorm extends Morris and Banfield's stay in Nebraska for a conference; Neela defends herself in court over a patient's death; and Alex and Sarah sneak out to a party.
Morris receives a package from his deceased father; Sam has concerns about removing Alex from the ventilator; and a woman with a high-risk pregnancy fears deportation.
Banfield treats two brothers injured during a drug deal, and later makes an important decision concerning the future of her family. Elsewhere, Neela tends to a young patient with sickle-cell anemia, prompting her to consider specializing in pediatric surgery; and communication breaks down between Gates and Sam regarding Alex.
Neela experiences a bizarre recurring dream about her efforts to save a girl with sickle cell anemia. Meanwhile, she also attends an interview and chances upon Dr. Elizabeth Corday (Alex Kingston, reprising her series role). And Gates treats a patient who jumped from a window while sleeping.
Morris treats a youngster who was hit while riding her bike. Meanwhile, Gates has trouble distancing himself from Sam, and Neela's nerves take over when she learns Brenner has returned from Australia.
Dr. Morgenstern (William H. Macy) visits County General upon learning a former mentor is seriously ill. Meanwhile, Sam's sister (Shannon Woodward) drops by unexpectedly; Gates and Morris treat an elderly man who was assaulted on the street; and Brenner is shocked by a patient's diagnosis.
Brenner tries to find a caretaker for the daughter of a woman who was severely injured in a car accident; Morris fights an insurance company that refuses to pay for a 78-year-old man's treatment. Meanwhile, Neela tells Brenner that she has received an offer from North Carolina. Eriq La Salle directed the episode.
Dr. Carter (Noah Wyle) surprises the staff with an unexpected visit. Meanwhile, Gates treats a groom with respiratory trouble that may be related to mushroom hunting; and Banfield tries to persuade her husband to have another child.
Carter (Noah Wyle) struggles with the new procedures and technology at County; Banfield and her husband look into adoption after in vitro fertilization proves frustrating; and Sam's mother (Amy Madigan) arrives at the ER in an altered state.
The doctors deal with relationship issues under the watchful eye of a film crew shooting a documentary on emergency medicine. Morris' girlfriend is rushed to the ER with gunshot wounds, Neela tries to understand her communication difficulties with Brenner, and Sam hopes to make amends with her mother (Amy Madigan). Noah Wyle guest stars.
On a mission to retrieve transplant organs for Carter, Neela and Sam fly to Seattle, where they meet with Hathaway (Julianna Margulies) and Ross (George Clooney), who are coordinating the transfer. But the donor's grandmother (Susan Sarandon) has second thoughts about the donation. Meanwhile, Benton (Eriq La Salle) watches out for Carter at Northwestern. Ernest Borgnine also guest stars.
Everyone seems to have forgotten that it is Neela's last day at County, but she proves herself ready to be an attending by standing her ground when she and Dubenko disagree on the approach to two surgical cases. Meanwhile, Brenner has a breakthrough about his painful past.
Morris and Brenner volunteer at Camp del Corazon, a camp for children who had open-heart surgery. Meanwhile, Banfield's adoption dreams slip away when a mother returns for the child she left at the ER. Tom Arnold guest stars.
In the series finale, old friends from County show up to support Carter as he opens a new medical facility for Chicago's less fortunate. Meanwhile, Gates treats a teen suffering from alcohol poisoning as a result of a drinking game; and an intern turns to Carter for help with a woman who has gone into labor with twins. Alexis Bledel and Ernest Borgnine guest star.