Prophylactic laparoscopic cholecystectomy should be performed in solid organ transplant patients with asymptomatic cholelithiasis. Modeled, decision analytic techniques were used to evaluate the different management strategies for asymptomatic cholelithiasis in cardiac and pancreas/renal transplant recipients. The clinical outcomes of expectant management, pretransplantation prophylactic cholecystectomy, and posttransplantation prophylactic cholecystectomy were analyzed for each population. The probabilities and outcomes were derived form a pooled analysis of published studies. One- and two-way sensitivity and cost analyses were performed. Prophylactic posttransplantation cholecystectomy is favored for cardiac transplant recipients with asymptomatic cholelithiasis, resulting in 5:1000 deaths versus 80:1000 for pretransplantation cholecystectomy and 44:1000 for expectant management. In distinction, expectant management for asymptomatic cholelithiasis is favored in pancreas/renal transplant patients, resulting in 2:1000 deaths compared with 5:1000 for prophylactic cholecystectomy. After heart transplantation, a strategy of routine, prophylactic cholecystectomy is anticipated to result in a cost savings of $17,779 per quality-adjusted life-year. Prophylactic posttransplantation cholecystectomy is the preferred management strategy for cardiac transplant patients with incidental gallstones, resulting in decreased mortality and significant cost savings per quality-adjusted life-year. Expectant management is the preferred strategy for pancreas and/or kidney transplant recipients with asymptomatic cholelithiasis.