Our objective was to describe the association that childcare burden, household composition, and health care utilization have with adherence to highly active antiretroviral therapy (HAART) among women in the United States. The primary outcome was 95% or more adherence to HAART evaluated at 10,916 semiannual visits between October 1998 and March 2006 among 1419 HIV-infected participants enrolled in the Women's Interagency HIV Study. HAART adherence levels of 95% or more were reported at 76% of the semiannual visits. At only 4% of the person-visits did women report either quite a bit or extreme difficulty in caring for child; at 52% of the person-visits women reported at least one child 18 years of age or older living in the household. We found a one-unit increase in the difficulty in caring for children (childcare burden was assessed on a 5-point scale: not difficult [1] to extremely difficult [5]) was associated with a 6% decreased odds of 95% or more HAART adherence (adjusted odds ratio [OR] = 0.94; p = 0.07). Each additional child 18 years of age or less living in the household was associated with an 8% decreased odds of 95% or more adherence (adjusted OR = 0.92, p = 0.03). Both the number and type of adult living in the household, as well as health care utilization were not associated with HAART adherence. Greater child care burden and number of children 18 years old or younger living in household were both inversely associated with HAART adherence. Assessing patients' difficulties in caring for children and household composition are important factors to consider when addressing adherence to HAART.