BACKGROUND: There are inconsistencies in the determinants of adherence to antiretrovirals (ARVs) across settings as well as a lack of studies that take into consideration factors beyond the individual level. This makes it necessary to examine factors holistically in multiple settings and populations while taking into consideration the particularities of each context, in order to understand the patterns of ARV adherence. This research explored ARV adherence and individual, relational and environmental-structural factors. METHODS: A cross-sectional survey was conducted from August 2008 through July 2009 among participants currently on ARVs recruited from 6 public health clinics, selected to maximize diversity in terms of caseload and location, representing the range of clinics within Rio de Janeiro city, Brazil. Multivariate logistic regression analysis was used to assess the association between our multilevel factors with ARV adherence among participants with complete cases (n = 632). RESULTS: Eighty-four percent of respondents reported adherence to all of their ARV doses in the last 4 days. Of the socio-demographic variables, those who had one child were positively associated with adherence (AOR 2.29 CI [1.33-3.94]). On the relational level, those with high social support (AOR 2.85 CI [1.50-5.41]) were positively associated with adherence to ARVs. On the environmental-structural level, we found gender was significant with women negatively associated with adherence to ARVs (AOR 0.58 CI [0.38-0.88]) while those with a high asset index (AOR 2.47 CI [1.79-3.40]) were positively associated with adherence to ARVs. CONCLUSIONS: This research highlights the importance of examining the multiple levels of influence on ARV adherence. Intervention research in lower and middle-income settings should address and evaluate the impact of attending to both gender and economic inequalities to improve ARV adherence, as well as relational areas such as the provision of social support.