Constipation is found in individuals with intellectual disabilities, autism, and cerebral palsy. Although generally a benign condition, it may lead to life-threatening intestinal obstruction, with or without volvulus, or to stercoral ulceration with enteritis and/or perforation. Two unusual cases of lethal chronic constipation are reported to demonstrate other very rare fatal mechanisms that may occur. Case 1: A 17-year-old male with cerebral palsy and autism was found deceased in bed. Death was due to pulmonary thromboembolism arising from compression of pelvic veins by acquired megacolon due to constipation (fecal mass 4.6 kg). Case 2: A second 17-year-old male with intellectual disability, global developmental delay, attention deficit disorder, seizures, and hypotonia collapsed and died during a medical evacuation from a remote community. Death was due to abdominal compartment syndrome in the context of medical air transport (medical retrieval), chronic constipation with acquired megacolon and megarectum (fecal mass 6.5 kg), global developmental delay, intellectual disability, and a suspected underlying genetic syndrome. These cases demonstrate that individuals with constipation may present for medicolegal assessment following sudden collapse/death and that pulmonary thromboembolism and abdominal compartment syndrome should be considered as rare possibilities in the evaluation of vulnerable individuals.