The keeping and breeding of ball pythons (Python regius) has grown tremendously in the last decade. Much of their popularity is related to the successful production of hundreds of desirable color morphs of these small, easy to care for pythons. In the early years of breeding, wild caught ball pythons were commonly introduced to breeding collections for genetic diversity and variability. With continued breeding success and the increased monetary value associated with genetic based color morphs most available ball pythons today are captive born and are second and third (or more) generation snakes. However, in some instances wild caught ball pythons are still being introduced to these established collections, and in combination with poor quarantine and biosecurity practices there has been an increase in gastrointestinal parasitism identified in these captive ball python collections. Routine fecal evaluations on live snakes in addition to gross necropsies and histopathology performed on deceased snakes is important in snake collection management. This scientific paper describes the incidence, clinical signs, patient evaluation and diagnostic techniques utilized including histopathological evaluation to identify gastrointestinal disease and mortality associated with the nematode parasite Strongyloides sp. in multiple collections of ball pythons in the United States. Treatment and collection management are discussed.