This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N = 174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44 = 3.1, p < 0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44 = 2.0, p > 0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88 = 5.97, p < 0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.