Background: The introduction of HAART has transformed HIV infection into a chronic manageable disease. The key to this success is the ability and willingness of HIV-positive individuals to adhere to HAART regimens. But at present little is known about the patient’s experience and adherence when taking such complex regimens. Objective: To assess the degree of adherence with antiretroviral therapy, identify which factors influence it, and describe the everyday experience of PLWHA on ARV therapy. Design and setting: We used a combination of methodologies, including questionnaires, interviews and medical record review with patients in selected hospitals. Patients and methods: For in-depth interviews, we purposively sampled 10 PLWHA. After screening for HIV- dementia each participated in an audio taped interview with the investigator. In the cross - sectional survey, consecutive HIV-infected patients at three ART centers in Addis Ababa were invited. Data on drug adherence were collected using patient self-report and depression was measured using Beck’s depression inventory (BDI). Clinical data were recorded by asking the patient and reviewing their chart. Knowledge about ART was assessed by questions presented in “Yes” or “No” format. Results: A total of 431 HIV infected patients responded to the survey questionnaire. 81.2% of patients were adherent by self report in the week before the assessment. The major reasons reported for non-adherence were, being too busy with other things or simply forgot (33.9%) and being away from home (27.5%). Correlates of adherence in the multivariate analysis controlling for sociodemographic differences were: having regular follow-up, not being depressed, having no side effects, fitting a regimen to the daily routine, being satisfied with the relationship with health care providers, and the perception that doctors were capable and had access to assistance and reliable pharmacy. Conclusions: The self-reported adherence rate in our study was higher than that seen in developed countries. Programs and clinical efforts to improve medication taking in the study setups should strive to: provide regular follow up for patients, manage depression with a multidisciplinary approach, increase patients’ awareness of the side effects of ARVs and possible remedies, integrate medications better into patients’ daily routines, improve patients' confidence, trust and satisfaction with their caregivers, eliminate problems of access, and alleviate the impact of cost