In Brief Objective: To assess whether antibiotic prophylaxis at urinary catheter removal reduces the rate of urinary tract infections. Summary of Background Data: Urinary tract infections are among the most common nosocomial infections. Antibiotic prophylaxis at urinary catheter removal is used as a measure to prevent them, albeit without supporting evidence. Methods: A prospective randomized study enrolled 239 patients undergoing elective abdominal surgery, who were randomized either for receiving 3 doses of trimethoprim-sulfamethoxazole at urinary catheter removal, or not. Urinary tract infections were diagnosed according to Center of Disease Control definitions. Urinary cultures were obtained before and 3 days after catheter removal. Subjective symptoms were assessed by an independent study-blind urologist. Results: Patients who received antibiotic prophylaxis showed significantly fewer urinary tract infections (5/103, 4.9%) than those without prophylaxis (22/102, 21.6%), P < 0.001. The absolute risk reduction for the occurrence of a urinary tract infection was 16.7%; the relative risk reduction was 77.5%, and the number needed to treat was 6. Patients with antibiotic prophylaxis also had less significant bacteriuria 3 days after catheter removal (17/103, 16.5%) than those without (42/102, 41.2%), P < 0.001. Conclusions: Antibiotic prophylaxis with trimethoprim-sulfamethoxazole on urinary catheter removal significantly reduces the rate of symptomatic urinary tract infections and bacteriuria in patients undergoing abdominal surgery with perioperative transurethral urinary catheters. Three doses of trimethoprim-sulfamethoxazole at urinary catheter removal significantly reduced the rate of urinary tract infections from 21.6% to 4.9% in patients undergoing elective abdominal surgery. We suggest this practice as a simple but effective measure to prevent a common complication in surgical patients.