An understanding of the main causes of mortality in caiman lizards (Dracaena guianensis) under managed care is imperative to promote optimal husbandry, health, and welfare. A retrospective review of morbidity and mortality in caiman lizards from North American zoological institutions between 2005 and 2020 was conducted. Postmortem data, including gross necropsy and histopathology findings, were available for 32 caiman lizards (n = 12 subadults, n = 20 adults) from six zoological institutions. Necropsy reports were evaluated to collect general demographic data, categorize cause of death (accident/trauma, congenital/genetic, degenerative/geriatric, infectious, deposition disease, neoplastic, unknown, and multifactorial), and assess common comorbidities. Infectious disease was the most common cause of mortality in adult lizards (8/20; 40%) with amoebiasis and bacterial etiologies being overrepresented. Demise due to traumatic/accidental injury was the second most common cause of death in adult lizards (3/20;15%) and included blunt force trauma or suspected drowning. Infectious disease (4/12; 33.3%) and trauma/accidental injury (4/12; 33.3%) were also the most common causes of death in subadults. The most common comorbidities or other incidental findings identified during necropsy included trematode parasitism (15/32; 46.9%), arteriosclerosis (11/32; 34.4%), and adrenocortical hyperplasia (6/32; 18.8%). This retrospective review suggests that management practices to prevent and control infectious diseases and mitigate traumatic injury play a pivotal role in the long-term care and survival of caiman lizards in managed care.