Females who ever had vaginal sex were interviewed annually in their first two years of college (n=386, ages 17 to 20 at study outset) and asked about risky sex behaviors and substance use. In year one, 60.2%(wt) had intoxicated sex, 31.4%(wt) had multiple sex partners, and 48.9%(wt) had unprotected sex (i.e., without a condom). At follow-up, high rates of persistence (86.0%, 52.7%, 78.8% respectively) and initiation (36.0%, 23.9%, 41.8%) were observed. In multiple logistic regression analyses, drug use and drinking were independently associated with having multiple sex partners. Intoxicated sex independently predicted condom non-use and multiple sex partners, and appeared to mediate the relationship between substance use and multiple sex partners. Implications for prevention and future research are discussed.