BACKGROUND: Zimbabwe is on track towards achieving viral suppression among adults (87%). However, adolescents have only achieved 44% by 2016. In Harare city, 57% of adolescents had attained viral suppression after 12 months on ART compared to 88% among adults. We determined factors associated with virological failure among adolescents (age 10-19 years) on antiretroviral therapy (ART) in Harare city. METHODS: We conducted a one to one unmatched case control study among 102 randomly recruited case: control pairs at the two main infectious disease hospitals in Harare. A case was any adolescent who presented with VL > 1000c/ml after at least 12 months on ART. A control was any adolescent who presented with VL < 1000c/ml after at least 12 months on ART. Interviewer administered questionnaires were used to collect data. Epi Info 7 was used to generate frequencies, means, proportions, ORs and p-values at 95% CI. RESULTS: We interviewed 102 case-control pairs. Poor adherence to ART [aOR = 8.15, 95% CI (2.80-11.70)], taking alcohol [aOR = 8.46, 95% CI (3.22-22.22)] and non- disclosure of HIV status [aOR = 4.56, 95% CI (2.20-9.46)] were independent risk factors for virological failure. Always using a condom [aOR = 0.04, 95% CI (0.01-0.35)], being on second line treatment [aOR = 0.04, 95% CI (0.23-0.81)] and belonging to a support group [aOR = 0.41, 95% CI (0.21-0.80)] were protective. CONCLUSION: Poor adherence, alcohol consumption and non-disclosure increased the odds of virological failure. Based on these findings support should focus on behavior change and strengthening of peer to peer projects to help address issues related to disclosure and adherence. Further operational research should aim to define other components of effective adherence support for adolescents with virological failure.