Examine long term sexual risk behaviors among persons who inject drugs (PWID) in New York City following implementation of “combined” prevention programming, including condom social marketing. Quantitative interviews and human immunodeficiency virus (HIV) testing were conducted among PWID entering Beth Israel Medical Center drug treatment programs 1990–2012. Data were analyzed by four time periods corresponding to the cumulative implementation of HIV prevention interventions. 7,132 subjects were recruited from 1990 to 2012; little change in sexual behavior occurred among HIV seronegative subjects, while HIV seropositive subjects reported significant decreases in being sexually active and significant increases in consistent condom use. HIV transmission risk (being HIV positive and engaging in unprotected sex) declined from 14 % in 1990–1995 to 2 % in 2007–2012 for primary sexual partners and from 6 to 1 % for casual partners. Cumulative implementation of combined prevention programming for PWID was associated with substantial decreases in sexual risk behavior among HIV seropositives.