This stark and thought-provoking drama delves into the trials and tribulations in the life of heroine addicts and delves into the ravages of this addiction through the story of a group of friends.
Mark Renton and Spud — known by his nickname – are running down Princes Street pursued by store security guards. Renton's circle of friends are introduced: amoral con artist Sick Boy, simple-minded, good-natured Spud – both also heroin addicts – clean-cut athlete Tommy, and sociopath Begbie, who picks extremely violent fights with people who get in his way.
Renton decides to quit heroin. He buys opium rectal suppositories from Mikey Forrester to ease the transition. After this final hit (and a violent spell of diarrhea caused by cessation of heroin) he locks himself into a cheap hotel room to endure withdrawal. He later goes with his friends to a club, finding that his sex drive has returned, and eventually leaves with a young woman named Diane. In the morning, he realises that Diane is a fifteen-year-old schoolgirl and that her "flatmates" are actually her parents. Horrified, Renton tries to shake the incident, but is forced to remain in touch after Diane blackmails him.
Sick Boy, Spud and Renton start using heroin again and Tommy, whose girlfriend dumped him after a chain of events initiated by Renton, begins using as well. One day the group's heroin-induced stupor is violently interrupted when Allison, their friend and fellow addict, discovers that her infant daughter Dawn has died from neglect without any of the group noticing. All are horrified and grief-stricken, especially Sick Boy, who is implied to have secretly been Dawn's father.
Renton and Spud are later caught stealing from a book shop and are pursued by security guards and arrested. Due to prior convictions Spud goes to prison, but Renton avoids punishment by entering a Drug Interventions Programme, where he is given methadone. Despite support from his family, Renton is depressed and bored, and escapes to his drug dealer's flat, where he nearly dies of an overdose. Renton's parents take him home and lock him in his old bedroom to force him through withdrawal. As Renton goes through severe withdrawal symptoms in his room, he has nightmares of Diane singing on the bed, his friends giving him advice and Allison's dead baby crawling on the ceiling. The heroin withdrawal is inter-cut with an imagined TV game show in which host Dale Winton asks Renton's parents questions about HIV. Renton is finally roused from his nightmares and hallucinations by his parents, who tell him he needs to get tested. Despite years of sharing syringes with other addicts, Renton tests negative.
Though clean of heroin, Renton is nevertheless bored and depressed. He visits Tommy, who has succumbed to addiction and is now severely ill and HIV positive. Renton moves to London and with a more professional image, starts a job as a property letting agent. He begins to enjoy his new life of sobriety and saves up money on the side while corresponding with Diane. However, soon Begbie, who has committed an armed robbery, and Sick Boy, who is now a pimp and drug dealer, show up at Renton's bedsit expecting to move in.
In Edinburgh, Tommy dies from HIV-related toxoplasmosis and the three travel back to Scotland for his funeral. While home, they meet Spud, who has been released from prison. Sick Boy suggests a profitable but dangerous heroin transaction, but needs Renton to supply half of the initial £4,000. After the purchase, Renton injects himself with a sample to test the heroin's purity. The four sell the heroin to a dealer for £16,000. During their celebration at a pub, Renton secretly suggests to Spud that they steal the money, but Spud is too frightened of Begbie to consider it. Renton finally has enough of Begbie after witnessing him glass and then beat a man who accidentally spilt beer over him. Early in the morning as the others sleep, Renton quietly takes the money. Spud sees him leave but does not tell the others. When Begbie awakens he destroys the hotel room in a violent rampage which attracts the police whilst Spud and Sick Boy flee.
Renton then vows to live a stable, traditional life. Later, Spud finds £4,000 Renton has left for him as Spud was the only member of the group who Renton felt sorry for.