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Abstract Objectives Indications for cholecystectomy have changed dramatically over the past three decades. Cystoisospora belli has been reported in cholecystectomy specimens of immunocompetent patients. The present study was designed to determine the prevalence and clinical association of C belli in the gallbladder. Methods The study included retrospective review of cholecystectomy specimens (n = 401) removed for various indications, and a prospective cohort of cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation. Correlations of presence of C belli with age, sex, clinical indication, and abnormalities of preoperative laboratory values were assessed by Fisher exact test. Results C belli was identified in 39/401 (9.7%) of the retrospective cohort, and 6/22 (27.3%) of the entirely submitted specimens. The presence of C belli showed no correlation with age, sex, clinical indication, or laboratory abnormalities. Conclusions C belli resides in a latent state in the gallbladder and may be best considered a commensal organism.