Background: Discontinuation of antiretroviral therapy (ART) reduces the immunological benefit of treatment and increases complications related to human immune-deficiency virus (HIV). However, the risk factors for ART discontinuation are poorly understood in developing countries particularly in Ethiopia. This review aimed to assess the best available evidence regarding risk factors for ART discontinuation in Ethiopia. Methods: Quantitative studies conducted in Ethiopia between 2002 and 2015 that evaluated factors associated with ART discontinuation were sought across six major databases. Only English language articles were included. This review considered studies that included the following outcome: ART treatment discontinuation, i.e. 'lost to follow up', 'defaulting' and 'stopping medication'. Meta-analysis was performed with Mantel Haenszel method using Revman-5 software. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals at a p-value of <0.05. Results: Nine (9) studies met the criteria of the search. Five (5) were retrospective studies, 3 were case control studies, and 1 was a prospective cohort study. The total sample size in the included studies was 62,156. Being rural dweller (OR = 2.1, 95%CI: 1.5-2.7,I2 = 60%), being illiterate (OR = 1.5, 95%CI: 1.1-2.1), being not married (OR = 1.4, 95%CI: 1.1-1.8), being alcohol drinker (OR = 2.9, 95%CI: 1.9-4.4,I2 = 39%), being tobacco smoker (OR = 2.6, 95%CI: 1.6-4.3,I2 = 74%), having mental illness (OR = 2.7, 95%CI: 1.6-4.6,I2 = 0%) and being bed ridden functional status (OR = 2.3, 95%CI: 1.5-3.4,I2 = 37%) were risk factors for ART discontinuation. Whereas, having HIV positive partner (OR = 0.4, 95%CI: 0.3-0.6, I2 = 69%) and being co-infected with Tb/HIV (OR = 0.6, 95%CI: 0.4-0.9, I2 = 0%) were protective factors. Conclusion: Demographic, behavioral and clinical factors influenced ART treatment discontinuation. Hence, we recommend strengthening decentralization of HIV care services in remote areas, strengthening of ART task shifting, application of seek-test-treat-succeed model, and integration of smoking cession strategies and mental health care into the routine HIV care program.