This study evaluated patient-initiated single-dose antibiotic prophylaxis and continuous long-term low-dose daily antibiotic use for the prevention of recurrent urinary tract infections (UTI) in 68 postmenopausal women. The women were randomized to take a low-dose antibiotic each night (continuous group, n = 37) or a single-dose antibiotic each time they experienced conditions predisposing to UTI (intermittent group, n = 31). During the 12-month study, 1.4 and 1.9 UTIs/patient developed in the continuous and the intermittent groups, respectively, which was significantly lower than the incidence of UTIs in the previous 12 months in these patients (4.7 and 5.1 UTIs/patient, respectively). The incidence of gastro intestinal adverse events was significantly lower in the intermittent group compared with the continuous group (9.1% versus 30.0%). In conclusion, patient-initiated single-dose intermittent antibiotic prophylaxis was as effective as low-dose daily antibiotic prophylaxis in the treatment of recurrent UTIs in postmenopausal women and was associated with fewer gastrointestinal adverse events.