Hooking up, or engaging in sexual interactions outside of committed relationships, has become increasingly common among college students. This study sought to identify predictors of sexual hookup behavior among first-year college women using a prospective longitudinal design. We used problem behavior theory (Jessor, 1991) as an organizing conceptual framework and examined risk and protective factors for hooking up from three domains: personality, behavior, and perceived environment. Participants (N = 483, 67% White) completed an initial baseline survey that assessed risk and protective factors, and nine monthly follow-up surveys that assessed the number of hookups involving performing oral sex, receiving oral sex, and vaginal sex. Over the course of the school year, 20% of women engaged in at least one hookup involving receiving oral sex, 25% engaged in at least one hookup involving performing oral sex, and 25% engaged in at least one hookup involving vaginal sex. Using two-part modeling with logistic and negative binomial regression, we identified predictors of hooking up. Risk factors for sexual hookups included hookup intentions, impulsivity, sensation-seeking, pre-college hookups, alcohol use, marijuana use, social comparison orientation, and situational triggers for hookups. Protective factors against sexual hookups included subjective religiosity, self-esteem, religious service attendance, and having married parents. Race/ethnicity, socioeconomic status, hookup attitudes, depression, cigarette smoking, academic achievement, injunctive norms, parental connectedness, and being in a romantic relationship were not consistent predictors of sexual hookups. Future research on hookups should consider the array of individual and social factors that influence this behavior.