This study attempted to measure anti-retroviral therapy (ART) adherence level in Zewditu Memorial Hospital, Addis Ababa. Retrospective and cross-sectional sources were used. Patient self-report adherence measuring tool was used. Based on this structured Patient self-report adherence questionnaire and in a simple random sampling technique data were collected from 138 clinical records of ART patients, exit- interviews were conducted on 50 ART patients and few ART providers. Descriptive, one sample t-test, correlation, uni-variate and multivariate logistic regression analysis were used. The findings revealed mixed adherence level (clinical data perspective 95-100% adherence rate found among 95% of the sample whereas in exit interview data analysis perspective 100% perfect adherence level was found among 30 respondents, suboptimal adherence rate which ranges from 29% to 86% found among 19 individuals whereas, one individual had 0% adherence/he didn’t took his ART for that week/. Waiting months on ART and regimen change were predictive factors for non-adherence behavior. Drug side effect/toxicity is a major reason for missed drug doses and regimen changing behavior. Forgetting, being busy, social stigma or discrimination, and alcohol use were the identified barriers for non- adherence behavior. Finally the study hints the necessity to design and practically implement substantive theories of behaviors based adherence interventions programmes that can promote adherence behaviors and alleviate the burdens of stigma or discrimination and drug side effects among ART patients.