We assessed risk of transmission among 4,016 HIV-infected patients in primary care, including men who have sex with men (MSM, n = 2,109), women (n = 1,104) and men who had sex with women (MSW, n = 803) in clinics in 15 cities across the U.S. A transmission risk act, assessed by computer assisted interviews, was defined as unprotected vaginal or anal sex with a partner who was HIV-uninfected or of unknown HIV status. MSM were more than twice as likely to report transmission risk acts than MSW (Odds Ratio [OR] = 2.35; 95% Confidence Interval [CI] = 1.84, 3.00; P < or = .001). Women were also more likely to report transmission risk acts than MSW (OR = 1.56; 95% CI = 1.19, 2.05; P < or = .001). Stimulant use was associated with transmission risk in all three groups (P < or = .05). MSM were more likely to use methamphetamines (8% versus 2% and 3% respectively), while MSW (17%) and women (12%, compared to 11% for MSM) were more likely to use cocaine. Clinical settings offer opportunities for preventing HIV transmission, particularly if interventions are tailored to sub-populations of HIV-infected patients.