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Obsessed with Tom Six's cult horror movie The human centipede (First sequence) (2009), middle-aged, overweight, asthmatic underground parking garage attendant Martin Lomax (Laurence R. Harvey) attempts to replicate Dr Heiter's (Dieter Laser) creation of a three-person centipede and collects victims for a 12-person centipede.

Human Centipede 2 is the second movie in director Tom Six's Human Centipede trilogy, preceded by The human centipede (First sequence) (2009) and followed by The human centipede III (Final sequence) (2015). Six wrote the screenplays for all three movies.

Since October 29th, 2011, (being released before the UK version, even though the conditions of censorship were announced later) a video-on-demand version (for example on Amazon Video) of the movie has been available. This version includes four cuts that cut out roughly three minutes of the movie. Unlike the UK version, the US version exclusively misses out on scenes with sexual content. On Amazon Video, it is listed as R-rated. However, since there's no special MPAA entry for it, it's highly doubtable that this is the accurate rating. It's rather likely that this version is based on the unrated US theatrical release. So far the uncensored version can be bought only directly from Bountyfilms.

In June 2011, the British Board of Film Classification (BBFC) rejected to rate the uncensored version of the movie, thus making it impossible to release it in the UK. However, the studio refuted the decision, and, in October, there were conditionally pleasant news that the BBFC rated a censored version of the movie with the highest possible rating, 18. Since November 21st, 2011, this version could be purchased on both DVD and Blu-ray Disc. The 30 cuts resulted in about 2.5 minutes of missing footage.