BACKGROUND: Nonmedical prescription opioid use has been linked to hepatitis C virus (HCV) infection among people who inject drugs and with using high dead space syringes that retain more blood and transfer more HIV if shared. Little is known regarding its effects on sex-risk behaviors. OBJECTIVES: This paper examines event-level associations between nonmedical prescription opioid use and sharing high dead space syringes (injection risk) and unprotected intercourse (sex risk) behaviors. METHODS: We recruited 1,985 participants from two overlapping risk groups-drug users and men who have sex with men (MSM)-and their sex partners. Participants completed an interview that included event-level sex questions with recent sex partners and injection questions with recent injection partners. We used multivariable generalized estimating equations (GEE) to assess the associations between nonmedical prescription opioid use and unprotected intercourse during sexual encounters and sharing syringes during injection episodes, while adjusting for within-person correlations. RESULTS: When both partners used nonmedical prescription opioids, its use was independently associated with unprotected intercourse in sexual encounters (OR = 2.24; 95% CI = 1.12, 4.49). The use of nonmedical prescription opioids was also associated with sharing high dead space syringes during injection episodes (OR = 6.57; 95% CI = 1.63, 26.51). CONCLUSION: Nonmedical prescription opioid use is associated with an increase in the risk of unprotected sex and sharing high dead space syringes. HIV and HCV prevention interventions for nonmedical prescription opioid users should address sex-risk behaviors and encourage the use of acceptable low dead space needles and syringes.