OBJECTIVE: Our objective was to evaluate screening for vesicoureteral reflux (VUR) among siblings of patients with VUR, in terms of cost, radiation exposure, and number of febrile urinary tract infections (fUTIs) averted. METHODS: We constructed a Markov model to evaluate 2 competing management options, that is, universal screening (cystographic evaluation of all siblings without symptoms) and usual care (cystographic evaluation of siblings only after fUTIs). Published data were used to inform all model inputs. Costs were estimated by using a societal perspective. RESULTS: Universal screening yielded 2980 fUTIs, whereas usual care yielded 6330. Therefore, universal screening for VUR in a cohort of 100,000 siblings 1 year of age without symptoms resulted in the prevention of 1 initial fUTI per 3360 siblings, at an excess cost of $55,600 per averted fUTI, in comparison with usual care. These estimates were heavily dependent on screening age and the effectiveness of antibiotic prophylaxis; prevention of a single fUTI would require screening of 166 siblings 5 years of age and 694 siblings 10 years of age. Similarly, if prophylaxis was ineffective in preventing fUTIs, then up to 10,000 siblings would need to be screened for prevention of a single fUTI. CONCLUSIONS: Prevention of a single fUTI would require screening of 30 to 430 siblings 1 year of age without symptoms, at an estimated excess cost of $56,000 to $820,000 per averted fUTI. These estimates are heavily dependent on screening age and the effectiveness of antibiotic prophylaxis.