Chelsea General is home to some of the top surgeons in the world, thanks in large part to the hospital's notorious Monday morning morbidity and mortality – or "311" – conferences. In these legendary meetings, Chief of Staff Harding Hooten leads a harsh, closed-door review of the complications encountered and mistakes made during the course of patient care. As the series opens, Trauma Chief Jorge Villanueva treats what appears to be an attempted suicide by car only to discover that the crash victim suffered a life-threatening brain aneurysm. Renowned neurosurgeon Dr. Ty Wilson is shaken by the case of 11-year-old Quinn McDaniels, whose soccer injury reveals a much graver problem. Workaholic Dr. Sydney Napur solves a case that had the rest of the hospital staff stumped. Meanwhile, Dr. Sung Park performs high-tech deep brain stimulation on a patient with uncontrollable hand tremors.

Sung, Hooten and Villanueva join forces to convince Trisha Miller, a 13-year-old girl with an advanced brain stem glioma, to try surgery one last time before giving up. Shaken from losing a patient, Ty turns to Dr. Tina Ridgeway for support. Meanwhile, Dr. Buck Tierney tries to bully resident Michelle Robideux into pronouncing a potential organ donor brain dead. And Sydney enlists Villanueva's help diagnosing a patient under the care of internist Dr. John Lieberman.

Tina's proposal to use an unorthodox procedure to treat a young man with extreme O.C.D. divides the surgeons at the 311 conference. At the same time, Villanueva must find a way to treat a girl with critical internal bleeding who refuses care because of her religious beliefs. Sung discovers that no good deed goes unpunished when a former patient sues him after her successful surgery creates an unforeseen side effect – abnormally increased sexual appetite.