Radical cystectomy is associated with the highest morbidity and mortality of all commonly performed urological cancer treatment procedures. Postoperative infection remains a major problem. We herein report the results of an open prospective study involving radical cystectomies, undertaken to evaluate the efficacy of 0.5/2 g tazobactam-piperacillin (TAZ-PIPC) in the prevention of postoperative infectious complications. Antimicrobial prophylaxis was performed using 0.5/2 g TAZ-PIPC (2.5 g i.v.) every 3 h during surgery and then twice a day for 3 days postoperatively. The patients were monitored to detect any postoperative infections. During surgery, irrigation fluid from the total abdominal cavity was taken for bacterial culture just before closing the abdomen. Surveillance cultures of drain discharge and urine from ureteral stents were also performed. Other samples were taken for bacterial culture when an infection was suspected. The total postoperative bacterial infection rate was 20.0% (7/35), and surgical site infection rate was 5.7% (2/35). These rates are lower than those documented in other studies. This study, even though open and noncomparative, showed that a short-interval regimen containing 0.5/2 g TAZ-PIPC provides adequate antimicrobial prophylaxis in patients undergoing radical cystectomy.