Several previous studies have suggested that hormonal contraception could be associated with increased risk of cervical infections. However, few high-quality prospective studies have examined this relationship. The goal of this study was to measure the effect of oral contraceptives (OC) and depot-medroxyprogesterone acetate (DMPA) on the acquisition of cervical chlamydial and gonococcal infections. Women attending 2 reproductive health centers in Baltimore, MD, were enrolled into a prospective cohort study. Participants were 15 to 45 years and were initiating OCs or DMPA or not using hormonal contraception. Interviews, physical examinations, and testing for incident cervical infections were conducted at 3, 6, and 12 months. The analysis included 819 women. Most were single (77%) and nulliparous (75%); 43% were black. Median age was 22 years. During the study, 45 women acquired a chlamydial or gonococcal infection (6.2 per 100 women-years). DMPA use (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.5), but not OC use (HR, 1.5; 95% CI, 0.6-3.5), was significantly associated with increased acquisition of cervical infections after adjusting for other risk factors. Cervical ectopy was not an important mediator of cervical infection risk. DMPA use, but not OC use, appeared to be significantly associated with increased acquisition of cervical chlamydial and gonococcal infections.