Background • Highly concentrated cranberry juice has long been considered to have protective properties against urinary tract infections (UTIs), on the basis of its content of cranberry proanthocyanidins, with A-type interflavan bonds. Objective • This study intended to evaluate the benefits of a highly concentrated cranberry juice for the prevention of repeated episodes of UTI in uncircumcised boys. Design • The study was a randomized, controlled trial. Setting • The study took place at Taipei City Hospital, Renai and Zhongxing Branches (Taipei City, Taiwan). Participants • Participants were 55 uncircumcised boys and 12 circumcised boys, aged 6 to 18 y, with histories of uncomplicated UTI, who were patients at the hospital. Intervention • The uncircumcised boys were randomly divided into 2 groups: (1) group 1 (n = 28) took 4 oz (120 mL) daily of cranberry juice for 6 mo; and (2) group 2 (n = 27), the negative control group, drank a placebo juice for 6 months. The circumcised boys in group 3, a positive control group, also drank a placebo juice for 6 mo. Outcome Measures • The time to UTI (ie, to the appearance of symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence to the treatment, and adverse effects were assessed at monthly visits. Results • After 6 mo of a prophylactic treatment with cranberry juice, the incidence of bacteriuria, mainly Escherichia coli, as shown in urine cultures at ≥1 × 105, were 25% (7/28), 37% (10/27), and 33.3% (4/12) in groups 1, 2 and 3, respectively. The comparisons of the rate of prevention of a recurrence of UTI between group 1 and group 2 and between group 1 and group 3 showed that group 1 had fewer recurrent episodes of UTI. No children withdrew from the study. No adverse events or side effects were recorded. Conclusions • Cranberry juice may reduce the number of repeated episodes of UTI in uncircumcised boys and may have beneficial effects against the growth of Gram-negative bacterial pathogens. Its preventive benefits against UTI in the uncircumcised boys were even higher than those of circumcision for the circumcised boys.