Purpose: To examine the association between religiosity (defined by frequency of engaging in religious/spiritual activities) and African-American adolescent females' sexual behaviors, attitudes toward sex, and ability to negotiate safer sex. Methods: Between December 1996 and April 1999, 1130 female adolescents were screened for eligibility in a sexually transmitted disease (STD)/human immunodeficiency virus (HIV) prevention trial. Data collection was achieved through a confidential self-administered questionnaire that examined religiosity and a structured interview regarding sexual behavior. Descriptive statistics were used to characterize the sociodemographics of the sample and logistic regression was used to measure the association between religiosity and the outcome variables. Results: In the study sample (n = 522), 64% of the adolescents had higher religiosity scores based on a 4-item scale (α = .68). Results indicate that adolescents who had higher religiosity scores were significantly more likely to have higher self-efficacy in communicating with new, as well as steady male partners about sex; about STDs, HIV, and pregnancy prevention; and in refusing an unsafe sexual encounter. These adolescents were also more likely to have initiated sex at a later age, used a condom in the past 6 months, and possess more positive attitudes toward condom use. Conclusions: Results from this study indicate a relationship between religiosity and sexual behaviors, attitudes toward sex, and ability to negotiate safer sex. © Society for Adolescent Medicine, 2003.