This study prospectively examined associations among multiple theoretically informed risk (e.g., depression, sexual sensation seeking, and risky peers norms) and protective factors (e.g., social support, STI knowledge, and refusal to have sex self efficacy) on unsafe sex among 715 African American adolescent females aged 15-21 who participated in an STI/HIV prevention intervention. Generalized estimating equation models were used to assess associations between baseline characteristics and sexual risk over a 12-month follow-up period. Overall risk in this population was high: at baseline, nearly a third of women reported sex under the influence of alcohol or substances; ≥ 2 partners for vaginal sex, and casual sex partners in the 60. days prior to baseline, and nearly 75% of those reporting vaginal sex used condoms inconsistently. In multivariable analysis, when risk and protective factors were simultaneously considered, higher levels of sexual sensation seeking were associated with having multiple sex partners and inconsistent condom use. Greater perception of risky peer norms was associated with a higher risk of having sex under the influence of alcohol or drugs. In addition, higher sex refusal self-efficacy was protective against having multiple; casual; and concurrent sex partners. Incorporating these salient factors into prevention programs may be critical to the development of targeted interventions for this population.