The aim of this study was to investigate the effects of transitioning from non-injection heroin use to injection drug use on sexual risk behavior. Non-injecting heroin users age 16-30 were enrolled from 2002 to 2005, and were re-interviewed at 6-month intervals for up to three years; 561 participants completed at least one follow-up interview. The majority of participants were non-Hispanic (NH) Black (54 %), 23 % were Hispanic, and 21 % were NH white. During follow-up, 154 participants (27.5 %) transitioned to injecting drugs. Logistic regression analyses were conducted using generalized estimating equations (GEE) to estimate the effect of transition to injection drug use on changes in sexual risk behavior during follow-up. Transition to injection drug use during follow-up was associated with increased likelihood of sexual risk behavior, especially for men. Harm reduction efforts that focus on preventing initiation or return to injection among non-injecting drug users may also ameliorate HIV sexual risk behaviors.