We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal (NM) therapy for preventing urinary tract infection (UTI) in postmenopausal women with recurrent UTI. Over a period of 9 months, 86 women received an estriol-containing vaginal pessary (0.5 mg estriol) twice weekly, and 85 women received NM (100 mg) once daily. We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM (P=.0003). Twenty-eight women (32.6%) who received estriol had no episodes of UTI versus 41 women (48.2%) in the NM group. There was a significant increase in the number of superficial cells in women who received estriol, whereas in the NM group, no such changes occurred. However, there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol. Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women.