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Background. We assessed factors associated with antiretroviral therapy (ART) adherence, including specific ART medications.Methods. The Strategies for Management of Antiretroviral Therapy study was an international antiretroviral therapy (ART) strategy trial that compared intermittent ART, using CD4+ T-cell count as a guide, to continuous ART. Adherence during the 7 days before each visit was measured using self-report. We defined high adherence as self-report of taking “all” pills for each prescribed ART medication; all other reports were defined as suboptimal adherence. Factors associated with adherence were assessed using logistic regression with generalized estimating equations.Results. Participants reported suboptimal adherence at 6016 of 35 695 study visits (17%). Factors independently associated with suboptimal adherence were black race, protease inhibitor–containing regimens, greater pill burden, higher maximum number of doses per day, and smoking. Factors independently associated with higher adherence were older age, higher education, region of residence, episodic treatment, higher latest (at the time of adherence) CD4+ T-cell count, and being prescribed concomitant drugs (ie, medications for comorbidities). Of specific drugs investigated, atazanavir, atazanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir were associated with suboptimal adherence, and tenofovir disoproxil fumarate/emtricitabine was associated with higher adherence.Conclusions. In this, the largest analysis of ART adherence to date, some protease inhibitor–containing regimens and regimens with >1 dose per day were associated with suboptimal adherence.