Abstract The purpose of this paper is to describe gender differences in risk behaviors—substance use and sexual behavior—in young adults with genital herpes. Two-hundred fifty-two young adults with genital herpes were recruited into the study via newspaper advertisements in a West Coast metropolitan area. As a part of a large randomized clinical trial, participants completed questionnaires measuring demographic characteristics and the risk behaviors of substance use and sexual behavior. Participants had a mean age of 27.1 years and were largely Caucasian, employed, college-educated, and heterosexual. Women were two years younger than men and had less income. Gender differences were found in both substance use and sexual behavior. Men were more likely to report current use of illicit drugs than were women. Men were also more likely to report a history of gonorrhea, and urethral discharge. Women reported initiating sex at an older age and having fewer sexual partners over their lifetimes than men. There were no gender differences in use of condoms or spermicides specifically to prevent transmission of genital herpes. Further study is needed of these young adults as they are at high risk for transmission of the disease and also for contracting other sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection. Sensitive interventions are needed with this high-risk population.