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Background: Adherence to antiretroviral therapy (ART) in HIV-positive adolescents (HPAs) is an enormous challenge in pediatric HIV management. Suboptimal adherence (OA) encourages treatment failure and HIV transmission. Several factors are inimical to OA, among HPA. Objective: The factors which influence adherence to ART in HPA accessing care in Nnewi, Nigeria, were determined. Subjects and Methods: One hundred and fifty HPAs, aged 10–19 years, who had been on ART for at least 6 months were recruited; 75 each for groups 10–14 and 15–19 years. Sociodemographic data were collected using interviewer-administered questionnaires. Relevant clinical data were retrieved from medical records, and current CD4 cell counts assayed. Results: There were 77 males and 73 females. OA to ART was defined as intake of ≥95% of antiretrovirals over a given period. Using pill count (PC), 74.7% (112/150) had OA. Using the preceding 28-day self-report (P28DSR), 84.0% (126/150) had OA, while for the preceding seven-day self-report (P7DSR), it was 89.3% (134/150). Factors significantly associated with sub-OA were tertiary education, missed clinic visits, travel time to facility ≤1 h, persistent feeling of sadness, and fear of death. Subjects with OA had a significantly higher rate of CD4 cell count recovery compared to those having sub-OA. Conclusion: Sub-OA is common in HPA and can be assessed with a combination of PC and preceding P28DSR, in resource-poor settings. As OA is crucial to CD4 cell count recovery, the latter can be useful in monitoring adherence in HPA.