The present study examined what factors were related to antiretroviral adherence for men and women who were HIV-seropositive. It was part of the HIV Epidemiologic Research on Outcomes (HERO) study that involved individuals in a methadone maintenance program. As part of the prospective cohort study, 113 participants were administered a baseline survey and then assessed for substance use and medication side effects once a month for up to six months. Adherence was measured using the medication event monitoring systems (MEMS). Seventy-four percent of participants were assessed at all six follow-ups with a median antiretroviral adherence rate of 62 percent across all of the follow-up visits. The participants were mostly male (53%), Hispanic (66%), unemployed (86%), and receiving public assistance (97%). Results illustrated that women had a significantly lower median adherence rate (46%) as compared to men (73%). Multivariate models run for males indicated that not being in a HIV support group, current usage of crack or cocaine, and side effects from medication were all related to worse antiretroviral adherence. For women, factors related to worse antiretroviral adherence were excessive alcohol use, current heroin use, and side effects from medication. When the model was run with the complete sample not having long-term housing or belonging to a support group, current usage of crack or cocaine, and medical side effects were related to worse adherence. The interaction between being female and excessive alcohol use also was related to worse adherence. The results suggest that stratifying for gender in analysis would provide valuable information in understanding antiretroviral adherence for men and women with HIV.