The pilot for the popular TV series is set during 24 frantic hours in the lives of a group of doctors, nurses, and staff members of a busy emergency room at a Chicago hospital. They deal with the seemingly endless casualties that stumble into their place of employment. The central characters are the chief resident and family man Dr. Mark Greene, who is considering a job in private practice due to pressure from his demanding law student wife Jennifer; outgoing Dr. Doug Ross, who deals with cases in his own personal way; straight-arrow Dr. Susan Lewis, trying to get by another long 36-hour shift; inexperienced third-year med student John Carter; cocky surgical resident Dr. Peter Benton; and troubled chief nurse Carol Hathaway.

Mark's wife arrives in the ER with the news that she has passed her bar exams but several members of the staff interrupt their intimate celebration. Greene treats an elderly woman whose husband isn't ready to let her go. It's been eight weeks since Hathaway's attempted suicide, but Doug Ross has yet to bring himself to visit the woman he went out with for two years. Susan Lewis saves a newborn who is brought into the ER choking. She also argues with the psychiatric attending who refuses to admit a patient suffering from dementia. Carter finds himself having to care for a group of German tourists who are suffering from food poisoning. He also treats a young flirt with a rash. Benton treats a recent surgery patient and finds his correct diagnosis overturned by the man's physician. Susan Lewis treats a family struck by a drunk driver. The husband and daughter will survive but there is little hope for the woman. The drunk driver is also brought in suffering from only a few scratches.

Carol Hathaway returns to work after her suicide attempt. Doug Ross still feels guilty about what happened. An ER patient found walking the streets takes to singing, constantly. Susan Lewis has a run-in with the cardiologist on duty, Dr. Kayson, when he disagrees with her treatment of a heart attack victim. At a case review session, she gets very little support from her colleagues. She also treats a woman who is dying of leukemia and who has good advice for Hathaway. Greene treats a woman who has obviously been beaten by her husband but can't get to agree to get help.

Susan Lewis has a run-in with Dr. Jack Kayson, the cardiology attending, when he accuses her of not providing him with all necessary information on a patient who subsequently died. He makes it very clear that Susan will bear all responsibility for his death. Her sister Chloe informs her that she and her boyfriend are moving to Texas. John Carter is still frustrated by Peter Benton's apparent lack of interest in teaching him anything but a new go for it attitude leads to an invitation to assist in a surgical procedure. Benton's sister suggests to him that the time has come for them to put their mother in a care home.

Benton is called out of surgery to find his senile mother.

Gates is assigned to the case of a closeted gay man whose partner clashes with his family; Neela meets her new surgical chief, Dr. Crenshaw; and Pratt must cope with the flood of new interns.

Abby and Kovac discover both the joys and difficulties of raising a newborn; Morris is wrongfully accused of being a child molester; Pratt has his trial-by-fire when he has to handle the ER alone, juggling multiple traumas, teaching duties and a troublesome intern. Neela continues to be the target of her difficult supervisor, and Sam discovers her sons latest extra-curricular activity.

Curtis Ames, a carpenter who suffered a stroke under Kovac's care, sues him for malpractice. Kovac and Ames square off in court as each man's recollections of Ames' treatment are recounted via testimony and flashbacks. Meanwhile, Abby returns to work and must adjust to the dramatic changes in her life, and Pratt's early morning trip to the barbershop results in a new awareness of community need. Also, Abby and Pratt try an unconventional method for treating a heart patient and Neela tries a risky procedure which doesn't sit well with her chief.

Kovac and Gates treat a girl who appears to have been assaulted. When the police are no help with Ames, Kovac decides to confront the problem himself; Morris and other doctors work on a patient with an ice pick in his ear. Meanwhile, Ray tries to keep his new relationship a secret and Pratt can't fully deal when his half-brother officially comes out. Also, a new male nurse arrives.

Weaver cares for a Katrina survivor who's reluctant to have surgery on her foot; budget cuts force Luka to make a difficult personnel decision. Also, Gates' home life intrudes on the ER; and Pratt and Hope are shaken after a patient in their care dies needlessly.

Kovac reacts negatively when he sees Abby giving extra attention to a patient; Ray and Gates clash over a patient, pinning Neela in the middle; and Ben takes things to the next level with Sam. Meanwhile, Pratt is under investigation and Weaver says a final goodbye to the ER.

Abby and Sam try to treat an aspiring comedian with mysterious symptoms; Pratt must defend his actions in front of the medical board; Neela scrubs in on a kidney donor transplant; and Morris, as the lone attending, must run a busy ER. Also, Kovac gets a surprising proposal from Abby.

Kovac and Gates deal with a hopeless father whose son succumbs to heart failure; Pratt tries to resolve the tension between him and his brother; an Armenian man tries to be a good samaritan but ends up crashing near the ER; Abby sneaks in baby Joe when she worries his sickness may be worse than it seems; Also, Sam injures the instructor of a self-defense seminar.

In 12 hours, the ER will shut down. As Kovac is under pressure to take care of the patients before the final hours, he makes a pivotal decision about his future. Meanwhile, Sam befriends a photojournalist who returns only this time she's terminally ill; Pratt is concerned when his brother ends up in the ER drunk; Morris confronts Gates when he ignores his orders and angrily sends him home while Gates tries to defend his actions.

What is supposed to be a departmental dinner organized by Kovac turns out to be the surprise of a lifetime for Abby when she learns it's a surprise wedding, secretly planned by the eager groom. Meanwhile, at the wedding, ER staffers enjoy themselves with music and booze while Neela finds herself the center of unexpected attention between Gates and Ray, which leads to a drunken fight and a shocking conclusion.