This study examined the relationship between prescription drug misuse and sexual risk behaviors (i.e. unprotected sex, increased number of sex partners) in a sample of young men who have sex with men (YMSM) in Philadelphia. Data come from a cross-sectional study of 18–29 year old YMSM ( N = 191) who misused prescription drugs in the past 6 months. Associations were investigated in two regression models: logistic models for unprotected anal intercourse (UAI) and zero-truncated Poisson regression model for number of sex partners. Of 177 participants engaging in anal intercourse in the past 6 months, 57.6 % engaged in UAI. After adjusting for socio-demographic variables and illicit drug use, misuse of prescription pain pills and muscle relaxants remained significantly associated with engaging in receptive UAI. No prescription drug class was associated with a high number of sex partners. This study provides additional evidence that some prescription drugs are associated with sexual risk behaviors among YMSM.