A man learns that his unusual stomach pains are being caused by a demon living in his intestines.
Duncan is an average guy who works at an average office job. But he starts to get pains in his stomach whenever he feels stressed out. Things get worse every time he tries to just hide his stress, by burying it inside. It all comes to a head when that "stress" is turned in to an actual little beast that exits his body via his butt and takes revenge on the things that stress him out. But it soon starts to threaten the one thing he loves, his wife.—Michael Hallows Eve
Chased by something unseen, Duncan Hayslip frantically runs down the street and into his mother's house. Duncan pleads with his wife Sarah to hide in the basement as his pursuer breaks down the door.
123 Hours Earlier - A sonogram shows a strange polyp inside Duncan's digestive tract. Doctor Yeager suggests that the colon lump is due to poor stress management. He refers Duncan to a therapist named Highsmith.
At work, Duncan's boss Phil reassigns Duncan from Accounting to Human Resources because Phil needs someone to conduct job terminations. Phil gives Duncan an office in the men's room where he will be working with Allistair. Duncan goes to see Highsmith, but nothing comes of the session.
Duncan and Sarah have dinner with Duncan's oversexed mother Beatrice and her young second husband Bobbi. Beatrice has also invited fertility doctor Lawrence Tip in an attempt to spur a pregnancy for her son and his wife. Allistair calls Duncan to tell him that he accidentally deleted an important file.
Back at home, Duncan retreats to the bathroom when his stomach becomes upset over the mounting anxiety. While his wife ignores the sounds with earplugs, a creature painfully emerges from Duncan's anus and renders him unconscious. The creature goes to the office and kills Allistair before returning to Duncan's colon.
The KRAC morning news reports Allistair's death, but attributes it to a rabid raccoon. Duncan reports to work and Phil has him begin the firings. Dr. Tip leaves Duncan a voicemail pressuring him to come to the fertility clinic. Duncan dreams that his intestinal creature attacks Dr. Yeager during a colonoscopy.
Duncan returns to Highsmith for a hypnosis session. The creature emerges from Duncan while he is under hypnosis and jumps out the window. Highsmith tells Duncan about an ancient myth regarding the anus. Highsmith theorizes that the creature emerges to kill when Duncan is stressed. It is the raw desire of his subconscious and Duncan should try relating to it.
The creature kills Dr. Tip in an alleyway after the man performs oral sex on a woman. It then returns to Highsmith's office, where Duncan dives it the name Milo, and it crawls back inside Duncan.
Duncan discovers a major account discrepancy at the office the next day. Phil coaxes Duncan to commit fraud as a coverup. The news reports Dr. Tip's death as another raccoon attack.
During a sock puppet session at Highsmith's, Duncan reveals a strained relationship with his father. Highsmith encourages him to make amends with his father Roger, who lives in a shack.
Duncan visits Roger and asks his father to come to therapy with him. He refuses. Due to the stress, Milo emerges while Duncan is in Roger's outhouse. Duncan convinces Milo to go back inside him and he will feed the creature when he returns to the office.
At work, federal agents seize all the of the office's records and assets. Duncan confronts Phil about the government investigation and learns that all of his money in the company is now lost. Duncan allows Milo to kill Phil in an elevator.
Sarah tells Duncan she is pregnant. Already stressed about the money and Phil's death, the untimely news causes Duncan to leave the house. Duncan and Milo bond while he lives on his own.
Duncan convinces Roger to participate in a session with Highsmith. When father and son engage in a heated confrontation, creatures emerge from both men. Roger's demon is named Ralph. Milo stabs Ralph, which in turn cripples Roger. When Milo learns that Duncan's wife is pregnant, the creature escapes out the window again. Realizing that Sarah and his unborn child are in danger, Duncan runs to his mother's house where Sarah is attending a party.
Duncan arrives in the opening scene and convinces Sarah to hide in Beatrice's sex dungeon basement. Milo eventually breaks into the house and uses the garbage disposal to enter the basement through the pipes. Milo attacks Sarah, but Duncan comes to her rescue. Sarah retreats to the backyard with the other partygoers. Milo pursues and the partygoers confront the demon with tiki torches.
Duncan arrives and chops off Milo's legs and an arm. Beatrice reveals that she knew Roger had a colon creature, but did not know it was hereditary. Duncan makes amends with Milo and the creature returns to his anus. Duncan apologizes to his wife.
Duncan opens his own financial consulting firm. Roger has become an invalid. Sarah's unborn child is revealed to be a boy and the child is shown to have a creature growing inside of it.
