Lindsay and Jenny, tourists from New York visiting Germany, get a flat tire on their way to a night club and seek help at the house of misanthropic, psychopathic surgeon Dr. Josef Heiter. He drugs the women with water spiked with Rohypnol and kidnaps them to a makeshift medical ward. Heiter kills a kidnapped truck driver after Heiter informs him he is "not a match". Heiter also abducts Japanese tourist Katsuro. Heiter is a retired world-renowned expert at separating Siamese twins, but dreams of making new creatures by sewing humans together. He says he will surgically connect his three victims mouth-to-anus, so that they share a single digestive system. His prior experiment, the 3Dog, conjoined three Rottweilers into a "Siamese triplet"; all three dogs died following the operation. Heiter has moved on to using human subjects. After Lindsay tries to escape and fails, Heiter decides to make her the middle part of the centipede, the most painful position for the healing process, as punishment. Heiter performs the surgery, placing Katsuro at the lead, Lindsay at the middle and Jenny at the rear; he removes both the upper and lower front teeth and lips of Lindsay and Jenny, and mutilates the buttocks of Katsuro and Lindsay to provide access to the rectums. He severs the ligaments of his victims' knees to prevent leg extension, forcing his victims to crawl. Once the operation is complete, Heiter takes the centipede to his living room, takes photos, and passes a mirror around for the segments of the centipede to view their new form. Heiter attempts to train his centipede as a pet by caging the centipede in a dog kennel, forcing Katsuro to eat dog food at dinner, and belittling Katsuro with racist insults and beating him with a crop when he becomes rebellious. When Katsuro defecates after apologizing to the girls, Lindsay is forced to swallow his excrement. Heiter becomes irritated after being kept awake by the screaming of a caged Katsuro (who, as the front part of the centipede, has his mouth free and is still able to speak, but in Japanese) and by the constant moaning of the women, threatening to remove their vocal cords. When the centipede attempts to escape while Heiter is swimming, all three segments are beaten with the crop. Heiter is displeased with the realization that Lindsay is constipated. He proposes to use laxatives on Lindsay. Before he can do this, he discovers that Jenny is dying from sepsis (suggesting that Lindsay may have already defecated into her mouth off-camera, which led to infection).