To examine the impact of a needle exchange program (NEP) on sexual risk behaviors of injecting drug users (IDUs). : Between 1997 and 2000, 889 IDUs in Chicago were recruited from NEPs and an area with no NEP into a cohort study. They were interviewed and tested for HIV at baseline and 3 annual follow-up visits. Random-effect logistic models were used to compare NEP users and nonusers regarding the number of sex partners, number of unprotected sex acts, and frequency of condom use. Compared to NEP nonusers, NEP users had a similar number of sex partners over time, but had 49% higher odds of using condoms with their main partners (P = 0.047). At baseline, there was no difference between NEP users and nonusers in episodes of vaginal intercourse, but over time the odds of having a higher number of unprotected instances of vaginal intercourse were reduced by 26% per year for NEP users but only 10% per year for nonusers (P = 0.02). This study suggests that NEP participation may help reduce the absolute risk of HIV sexual transmission.