This study examined the impact of changes in self-efficacy over time on HIV-related injection and sex risk behaviors among Puerto Rican drug injectors and crack smokers. Baseline (T1) and 6-month follow-up (T2) data were collected between 1998 and 2000 in New York and Puerto Rico (follow-up rate=79%, 952/1199). Differences in scores on self-efficacy (for risk behaviors) between T1 and T2 were first computed and dichotomized (negative change vs. no/positive change). Those with negative change in self-efficacy were more likely than those with no/positive change to engage in HIV injection and sex risk behaviors at T2. The relationships were significant in multiple logistic regressions after controlling for the effects of potential confounding variables. The findings indicate that improving perceived self-efficacy for risk reduction can help reduce HIV transmission behaviors in high-risk drug users. HIV/AIDS prevention programs should include a focus on enhancing self-efficacy for reducing risk behaviors.