The Amur leopard (Panthera pardus orientalis) is one of the most critically endangered leopards on the International Union for the Conservation of Nature red list. The primary objective of this retrospective study was to identify common and significant causes of morbidity and mortality in the North American Amur leopard zoo population. This information provides insights that contribute to their improved care, health, and medical management and, ultimately, affects the sustainability of this leopard subspecies in the wild. Medical records and complete postmortem reports were requested from all North American zoologic institutions that held Amur leopards in their collections from 1992 to 2014. Information from 175 individuals, representing 93% of the population (188 animals), was received. Data were reviewed generally and by subdivision into the following age groups: neonate: 0 day–3 mo (n = 45); juvenile-young adult: 3 mo–5 yr (n = 21); adult: 5–10 yr (n = 17); senior: 10–15 yr (n = 31); or geriatric: >15 yr (n = 61). The major causes of morbidity, listed by body system for the study population, excluding neonates, were musculoskeletal (40%), reproductive (24%), dental (19%), cardiopulmonary (13%), gastrointestinal (13%), and urogenital (12%). The two most common causes of death or euthanasia, primarily in senior and geriatric animals, were chronic renal disease and neoplasia; maternal neglect and maternal trauma were most common in neonates. The largest populations in this study were neonates and geriatrics, indicating that if animals survive the neonatal period, they often live into their late teens to early 20s. This is the first comprehensive study of the causes of morbidity and mortality in the Amur leopard zoo population in North America.