The objectives of this study were to measure the prevalence of adherence to drug treatment and analyze associations with characteristics pertaining to the treatment, disease, health professionals and services, and socio-demographic issues in patients with systemic lupus erythematosus (SLE) in the city of Rio de Janeiro, Brazil. A sample of 246 women with SLE was analyzed. The data were collected through individual interviews and a review of patient charts. Adherence was estimated according to the Morisk criteria, and the associated factors were analyzed by hierarchical modeling. The percentage of patients classified as adherent to treatment was 31.7%. The reasons cited for non-adherence were: carelessness with drug administration times (52.43%), forgetfulness (38.21%), adverse drug reaction (13.8%), and interruption of treatment due to improvement in symptoms (7.72%). Factors associated with adherence were: behavior towards the presence of adverse drug reaction, hematological alterations, presence of mucocutaneous manifestations, legibility of the medical prescription, schooling, and family support. The study concludes that adherence to drug treatment in SLE is a complex and multifactorial phenomenon, and the results corroborate findings from studies conducted in developed countries. The hierarchical modeling proved to be a good alternative for evaluating adherence, since it allowed visualizing the various stages in the analysis.