Appointment In Samarra is the 11th episode of Season 6. It aired on December 10th, 2010.
Dean seeks out Death to help get Sam's soul back. Death tells Dean he will help Sam if Dean will agree to act as Death for 24 hours. Meanwhile, Sam decides he doesn't want his soul back and asks Balthazar for a protective spell to keep his soul out of his body. Balthazar tells Sam he needs the blood of his father for the spell to work, and since John Winchester is dead, Sam decides Bobby is the next best thing.
Dean goes to see an old acquaintance of his father, Dr. Robert. Dean pays the doctor and his assistant, Eva, to kill him and then bring him back to life. After the doctor claims a 75% success rate for the procedure, Dean gives him a letter addressed to Ben and asks him to mail it in case something goes wrong. Dr Robert takes the letter and then tells Dean he has 3 minutes of death before injecting him with something that kills him. Dean, once his soul has left his body, says a spell that summons the reaper Tessa. He tells Tessa to contact her boss, Death, and let him know that Dean wants to talk to him. She refuses, but, to their mutual surprise, Death appears behind them and greets Dean.
Dean tries to make a deal with Death to get Sam and Adam Milligan's souls out of Lucifer's Cage. Dean tells Death that he'll return his ring to him in exchange for their souls, but Death reminds Dean that he was only supposed to be borrowing his ring in the first place, and anyways, he knows where Dean hid it. He doesn't completely reject Dean's request, however; he tells Dean that he has to make a choice between Sam or Adam's soul. Dean chooses Sam, and Death tells him that he can return Sam's soul to him, even putting Sam's time in hell behind a wall in his mind, but only if Dean wins their wager: Dean has to wear Death's ring and be Death for a day. If he takes the ring off, he loses the wager and Sam's soul stays in hell. Before Dean can learn why Death wants him to take his place for a day, Dr Robert revives him.
Dean tells Sam and Bobby about his wager with Death, but Sam is opposed to the idea. He doesn't want his soul returned to his body, especially because the "wall" Death proposes to put up in his mind isn't necessarily permanent. He tries to get to the ring before Dean, but fails, and Dean asks Bobby to watch Sam before leaving. After Dean puts on the ring, he appears somewhere else entirely and Tessa is there. She tells Dean that for the next 24 hours, he has to touch and kill everyone who's on her list so that she can reap them.
While Dean is with Tessa, Sam slips Bobby and summons Balthazar. He asks Balthazar for a way to keep his soul out of his body, and Balthazar, who wants to screw Dean over and have Sam in his debt, gives Sam the spell "for free." He also tells Sam that he has to make his body, aka Vessel, uninhabitable for his soul by committing patricide. He "needs the blood of his father, but his father needn't be blood," so Sam resolves to kill Bobby. Bobby realizes what Sam is up to, however, and hits him over the head. Unfortunately, Sam vanishes before Bobby can tie him up. Bobby locks the door to the basement and then locks himself in the closet, where Sam quickly finds him. Sam breaks through the door with an ax, but Bobby has set a trap door outside the closet that drops Sam into the basement. Bobby asks Sam what he's doing through the basement door, but Sam doesn't explain. He escapes the basement and Bobby tries to track him, but Sam gets the jump on him and knocks Bobby unconscious.
Meanwhile, Dean and Tessa are busy killing and reaping souls. The first is an armed robber who is shot by a store clerk during a holdup, and the second is an overweight man who had a heart attack. Dean doesn't have a problem killing either man, but he is unable to kill the next person, a 12-year-old girl with a heart condition. He refuses to let her die, telling Tessa that there's no such thing as fate or destiny. Because he doesn't touch the girl, her heart miraculously heals so the surgeon and his nurse, Jolene, go home early. This changes the course of destiny, and Jolene is injured so badly in a car accident (which wouldn't have happened had she stayed to operate on the girl) on the way home that Dean is forced to kill her and Tessa reaps her soul "decades early." The nurse's husband, Scott, is then so distraught that he drinks and drives and almost crashes into a busload of people--the accident is averted at the last minute when Dean takes off Death's ring and jerks the wheel of Scott's car. Dean saved his and other's lives, but because he took off the ring he lost his wager with Death. Tessa tells him that it's over, but he still goes back to the hospital and kills the 12-year-old girl because he has learned his lesson: you can't mess with destiny or the "natural order" without setting off a chain reaction that has untold consequences.
Tessa takes him back to Bobby' house, where he is just in time to stop Sam from killing Bobby. They restrain him in Bobby's Panic Room, and Dean is distraught because he can't keep Sam locked up forever. Death then shows up at Bobby's house to get his ring back. He speaks to Dean about his failed tenure as Death, and is pleased that Dean learned his lesson about cheating death and disturbing the natural order. Even though Dean was unable to keep his ring on for a full 24 hours, Death decides to retrieve Sam's soul. He tells Dean that he needs to keep digging on the topic of souls before going to Hell and coming back with Sam's soul. The episode ends with Sam screaming as Death returns his soul to his body.