Introduction non-adherence to antiretroviral therapy (ART) constitutes the main cause of therapeutic failure among HIV-infected adolescents, especially in the aged group 15 to 19 years. We aimed to determine factors associated with this non-adherence in this specific population. Methods we conducted a cross-sectional study at the Mother and Child Center in Yaounde from August to October 2018. Delayed clinic appointment was referred to as defaulters. Non-adherence was measured during the 3 days preceding inclusion by self-reported method following quantitative (missing dosage of ART), qualitative (ART taken with a delay of more than 2 hours) and combined measure. A threshold of non-adherence > 20% was considered high, with p<0.05 statistically significant. Results overall, 195 out of 251 (77.7%) eligible adolescents were included, of which 56.9% were girls (sex-ratio = 4/3). The mean age was 16.8 ± 1.5 years. The rate of defaulters was 21.0%. Following quantitative approach, 33.8% were non-adherent. Using combined approach, we had 41.0%. This non-adherence was associated with duration on ART > 5 years (adjusted Odds Ratio [aOR]: 2.33;95% Confidence Interval [CI]: 1.08-5.00; p:0.030), defaulters (aOR: 2.56;95% CI: 1.12-5.82; p:0.025) and HIV Viral Load (VL) ≥ 40 copies/ml (aOR: 0.42; 95% CI: 0.21-0.83; p:0.013). Conclusion at this reference pediatric center, 4 out of 10 adolescents aged 15-19 years on ART are non-adherent, driven by missing dosage of drug intake. Strategies for enhanced adherence for late age adolescents are therefore warranted, by prioritizing interventions on defaulters and duration on ART > 5 years.