BACKGROUND: Urinary tract infection is the most frequent health care-associated complication. We hypothesized that the implementation of a multifaceted prevention strategy could decrease its incidence after surgery. METHODS: In a controlled, prospective, before-after intervention trial with 1328 adult patients scheduled for orthopedic or abdominal surgery, nosocomial infection surveillance was conducted until hospital discharge. A multifaceted intervention including specifically tailored, locally developed guidelines for the prevention of urinary tract infection was implemented for orthopedic surgery patients, and abdominal surgery patients served as control subjects. Infectious and noninfectious complications, adherence to guidelines, and antibiotic use were monitored before and after the intervention and again 2 years later. RESULTS: The incidence of urinary tract infection decreased from 10.4 to 3.9 episodes per 100 patients in the intervention group (incidence-density ratio, 0.41; 95% CI, 0.20-0.79; P=.004). Adherence to guidelines was 82.2%. Both the frequency and the duration of urinary catheterization decreased following the intervention. Recourse to antibiotic therapy after surgery dropped in the intervention group from 17.9 to 15.6 defined daily doses per 100 patient-days (P<.005) because of a reduced need for the treatment of urinary tract infection (P<.001). Follow-up after 2 years revealed a sustained impact of the strategy and a subsequent low use of antibiotics, consistent with stable adherence to guidelines (80.8%). CONCLUSIONS: A multifaceted prevention strategy can dramatically decrease postoperative urinary tract infection and contribute to the reduction of the overall use of antibiotics after surgery.