We evaluated and compared 81 urinary tract infections (UTIs) with Staphylococcus saprophyticus occurring in 72 college women with Escherichia coli UTIs. During the 14-month study period, S saprophyticus was the second most common cause of UTIs, accounting for 11% of the total. Staphylococcus saprophyticus infections occurred more frequently during the late summer and early fall. Age, history of previous UTI, signs and symptoms of infection, and findings on urinalysis were similar in patients with S saprophyticus and E coli infections. Nine (41%) of 22 S saprophyticus infections were localized to the upper urinary tract by the antibody-coated bacteria technique compared with 18 (16%) of 115 infections with E coli (P = .01). Rectal, vaginal, and urethral colonization with S saprophyticus was associated with UTI caused by these organisms, suggesting that their pathogenesis resembles that of E coli UTIs. In vitro susceptibility testing showed almost uniform sensitivity of S saprophyticus to most antimicrobials used to treat UTIs, but recurrent infections occurred in six of the 72 women despite adequate therapy. Physicians and microbiologists must be aware that S saprophyticus is an important cause of UTIs in young women.