Objectives: Previous studies have shown that HIV-positive women underuse highly active antiretroviral therapy (HAART), but the reasons for this gender disparity are not completely understood. We examined whether one reason for this disparity is that women are less likely to use HAART when they have difficulty taking HIV medications openly at home. Methods: This was a prospective cohort study of a national probability sample of 2864 adults receiving HIV care. Results: Among the 1910 people who participated in the follow-up survey and reported taking HIV medications, 11.8% reported they could not take HIV medications openly at home. Those who reported they had difficulty taking medications openly at home were more likely to be women, to be black, to live in the northeast United States, to have an annual income <$5000, and to have no health insurance. In bivariate analysis, women had twice the odds of reporting difficulty taking medications openly (odds ratio [ OR] 2.07, 95% confidence interval [CI] 1.36-3.15) compared with gay/bisexual men, although this gender difference was no longer significant in the adjusted model. For women, having difficulty taking medications openly at home was associated with a substantial decrease in the probability of being on HAART in the adjusted model (0.59, 95% CI 0.47-0.70 vs. 0.78, 95% CI 0.74-0.83), whereas no significant differences were observed for heterosexual or gay/bisexual men. Conclusions: These results suggest that having difficulty taking medications openly is a barrier to antiretroviral treatment among women, but not among men, and may contribute to gender disparities in HAART use.