The study was conducted to compare rates of sexually transmitted diseases (STD) and side effects in a cohort of high-risk women who received either an intrauterine device (IUD) or depo-medroxyprogesterone acetate (DMPA). We performed a retrospective chart review study of women seeking contraception at an innercity resident obstetrics/gynecology clinic. We compared 194 women with IUDs vs. 191 women receiving DMPA. Mean age was 31.9 years, with 75.1% and 69.2% being nonwhite and single, respectively. More white women received the IUD (34.5% vs. 15.0%, p < 0.001), and significantly more single women received DMPA (85.2% vs. 53.9%, p < 0.001). After controlling for potentially confounding variables, DMPA women were significantly more likely to have a subsequent STD, although this effect disappeared when interaction terms were added to the model. Overall, duration of contraception use and being black were the best predictors of subsequent STD infection. Women who received IUDs were more likely to report side effects but less likely to discontinue use of their birth control (18.8% vs. 67.0%, p < 0.001). Although sexual risk factors may have influenced provider prescribing practices in selecting IUD or DMPA, overall rates of STDs and discontinuation rates for IUDs were equivalent or superior to rates for DMPA.