Roger Ebert refused to assign this film a star rating for his review (not to be confused with giving it a zero star rating, which he hands out to the very worst films that he sees), saying it doesn't really matter whether the film is perceived as good or bad. He closes the review by writing, "[The film] is what it is and occupies a world where the stars don't shine."
When approaching investors prior to filming, the filmmakers told them they wanted to make an international horror film that involved stitching people together but did not mention how exactly they would be stitched, fearing the mouth-to-anus aspect would put the investors off.
Although the film is set in Germany, filming took place in the Netherlands due to the countries' similar landscapes. Heiter's home, where most of the film takes place, was a villa in the Netherlands found by the production team. The property was in a residential area and not surrounded by woodland as it appears in the film, but by other houses, so the filmmakers had some difficulty ensuring the other houses did not appear in shot. Real hospital beds and intravenous drips were rented from a local hospital.
Josef Heiter's first name references Josef Mengele, a Nazi doctor who carried out torture experiments on prisoners in Auschwitz concentration camp. The surname Heiter, literally meaning "cheerful" in German, is a reference to lesser-known Nazi war criminals, doctors Fetter and Richter.