Background: Adherence to antiretroviral therapy (ART) has paramount advantages for programmatic success, including its good treatment outcomes and reduced risk of resistant viral strains transmission to the general population. There is limited evidence on the magnitude and associated factors of adherence to ART among adult PLWHA attending highly active ART (HAART) at Adare General Hospital, Southern Ethiopia. Objective: This study aimed to determine the magnitude and associated factors of adherence to ART among adult PLWHA attending (HAART) at Adare General Hospital, Southern Ethiopia. Methods: A hospital-based cross-sectional study was conducted from January 01/2018 to February 30/2018 at Adare Hospital. The participants were 370 adult people living with HIV/AIDS taking ART and who were selected by systematic random sampling technique. The data were collected by trained health professionals using a pre-tested interviewer-administered structured questionnaire. The data collected was entered into a computer and analysed using SPSS version 19. Descriptive statistics and multiple logistic regressions were applied. The significance level of association was considered at p-value <0.05. Results: The magnitude of retrospectively self-reported combined adherence (measured by dose, schedule and dietary instructions) to ART in the past seven days before the interview was 80.3%. In multivariate analysis, Sidaamu Afoo language (AOR=0.5, 95%CI: 0.21-0.99), monthly income <1,000 Ethiopian Birr (AOR=0.08; 95%CI: 0.030.26), not disclosing HIV status to others (AOR=0.18; 95%CI: 0.07-0.50), taking ART pills comfortably while others looking (AOR=6.0; 95%CI: 2.54-13.91) and no utilisation of reminders (AOR=0.08; 95%CI: 0.03-0.21) were factors significantly associated with combined adherence. Forgetfulness and not wanting to take ART while others are looking were major reasons to miss pills. Conclusion: Adherence to ART among adult PLWHA attending HAART at Adare Hospital was suboptimal, but still comparable with that of resource-limited settings. To maximise treatment success, considering emphasised translation to Sidaamu Afoo language, encouraging patients to be involved in any income-generating system and to reveal their HIV status for others is helpful. [Ethiop. J. Health Dev. 2020; 35(2):000-000]