College students are engaging in high rates of behavior related to risk of infection from Human Immunodeficiency Virus (HIV) and other sexually transmitted diseases (STDs). A cognitive-behavioral skills training program for heterosexual college females focused on sexual assertiveness skills and the reduction of risk-related behaviors was designed and evaluated compared with an education-only program. Participants completed pre-intervention, post-intervention, and one-month follow-up assessments of: (a) HIV/STD-related knowledge and beliefs; (b) sexual, alcohol, and drug-related behaviors; and (c) sexual assertiveness role-plays. Skills training participants compared to education-only participants scored higher on sexual assertiveness skills, specific knowledge of HIV infection, and self-efficacy to perform lower risk sexual behaviors and reported a reduction in risk-related behaviors at post-intervention and follow-up assessments. The effectiveness of behavioral skills in HIV risk-reduction programs for college students is discussed.