Background: Virologic failure is a persistently detectable viral load exceeding 1000copies/ml after at least six months of starting a new anti retroviral treatment. Globally, it is targeted for 73% of all people living with Human Immunodeficiency Virus to be virally suppressed by 2020. But surveys reveal that viral load suppression prevalence is much lower than the target. Beside with identifying those virologically failed patients in the region and in the study area, it is important to identify the determinants of virologic failure. Objective: To identify determinants of Virologic failure among adults on first line highly active anti retroviral therapy at public health facilities in Kombolcha town, North East, Ethiopia, 2019. Methods: An institution based unmatched case control study design was conducted from April to May/2019. About 130 cases and 259 controls were selected by simple random sampling. Data were extracted from charts of patients’ using structured checklist. Multivariable logistic regression analysis was made to identify possible factors. Hosmer-Lemeshow goodness of fit test was used to check the model. Finally, independent predictor variables of virologic failure were identified based on the adjusted odds ratio with 95% CI and p-value of 0.05. Results: The odds of Virologic failure were 2.4 folds (AOR=2.44, 95% CI: 1.353, 4.411) higher in clients aged less than 35 years compared with those older clients. The odds of virologic failure were five folds (AOR=5.00, 95% CI: 2.60, 9.63) higher in clients who did not disclose their HIV status. The odds of Virologic failure were three folds (AOR=2.99, 95% CI: 1.33, 6.73) higher in clients with poor adherence. The odds of Virologic failure were 7.5 folds (AOR=7.51, 95% CI: 3.98-14.14) higher in clients who had recent CD4 count of ≤ 250 cells/ mm3. Conclusion and recommendation: This study revealed that age, marital status, occupation, disclosure status, baseline functional status, missed clinic visit, current ART regimen, adherence for treatment and recent CD4 count were found to be significantly associated with Virologic failure. Therefore, adherence support should be strengthened for clients that will reduce their miss in clinic visit which intern helps for better treatment adherence resulting in boosting immunity and suppress viral replication. Key words: ART, Determinants, Virologic failure, Kombolcha Town.