Medication adherence and antiretroviral therapy retention are required for successful durable, virologic suppression and treatment outcomes among youths. The use of peer-led health education in increasing medication adherence and antiretroviral therapy retention has been advocated. Therefore, this study investigated the effect of peer education on medication adherence and antiretroviral-therapy retention practices among Youth Living with HIV in Niger state, Nigeria. The study was a quasi-experimental design in two selected hospitals. One hospital was assigned to a one-hour peer-led health education session for six weeks, and the 2nd served as the control group. Data were collected at baseline, immediate post-intervention, and at the sixth-week follow-up. Data were analyzed using descriptive and inferential statistics at a 0.05 level of significance. Majority of respondents practice Islam and are within the ages of 20-24 years (control: 100%, 89%; intervention: 83%, 73%), from the Hausa Ethnic group (control: 62%; intervention: 56%). Majority of respondents in the control group have Islamic education (50%) and Secondary education (50%), while the majority of those in the intervention group have primary education (35%), secondary (29%), tertiary (19%) and Islamic (17%) respectively. Medication adherence and ART retention was higher in the intervention group (27%, 16%) compared with the control (17%, 9%). A significant association between knowledge and perception due to peer education on medication adherence was found (24%, 80%) in the intervention group and (11%, 36%) in the control group. Subsequently, the 6th week follow-up sustained findings from the intervention period on medication adherence and ART retention (27%, 16%) in the intervention group compared with control group (17%, 9%). Similarly, knowledge and perception follow-up post intervention was sustained (24%, 80%) in the intervention group and (11%, 36%) in the control group. Interventions leveraging peer-led health education enhanced HIV medication adherence and antiretroviral therapy retention practices among youths. Thus, we recommend scale-up of the structured peer-led curriculum and integration into the health systems to improve health outcomes among HIV positive youths, achieve epidemic control and accelerate progress for the UNAIDS 95:95:95 goals.