POPULATION: Spinal cord injury (SCI) patients with neurogenic bladder have an increased risk for symptomatic urinary tract infection (UTI). Recurrent UTI requires multiple courses of antibiotic therapy, markedly increasing the incidence of multidrug-resistant (MDR) bacteria. METHODS: During an observational prospective study, we determined the safety and efficacy of a weekly oral cyclic antibiotic (WOCA) regimen to prevent UTI in SCI adult patients with neurogenic bladder undergoing clean intermittent catheterization. The WOCA regimen consisted of the alternate administration of an antibiotic once per week over a period of at least 2 years. The antibiotics chosen were efficient for UTI, well tolerated and with low selection pressure. RESULTS: There was a significant decrease in antimicrobial consumption linked to the dramatic decrease in the incidence of UTI. Before intervention, there were 9.4 symptomatic UTIs per patient-year, including 197 episodes of febrile UTI responsible for 45 hospitalizations. Under the WOCA regimen there were 1.8 symptomatic UTIs per patient-year, including 19 episodes of febrile UTI. No severe adverse events and no new cases of colonization with MDR bacteria were reported. CONCLUSIONS: In this prospective, observational pilot study a novel approach to the prevention and treatment of UTI in SCI was investigated. Our study shows the benefit of WOCA in preventing UTI in SCI patients.