AbstractWe followed adolescents and adults living with HIV aged older than 15 years who enrolled in a South African private-sector HIV programme to examine adherence and viral non-suppression (viral load > 400 copies/mL) of participants with (20,743, 38%) and without (33,635, 62%) mental health diagnoses. Mental health diagnoses were associated with unfavourable adherence patterns. The risk of viral non-suppression was higher among patients with organic mental disorders [adjusted risk ratio (aRR) 1.55, 95% confidence interval (CI) 1.22–1.96], substance use disorders (aRR 1.53, 95% CI 1.19–1.97), serious mental disorders (aRR 1.30, 95% CI 1.09–1.54), and depression (aRR 1.19, 95% CI 1.10–1.28) when compared with patients without mental health diagnoses. The risk of viral non-suppression was also higher among males, adolescents (15–19 years), and young adults (20–24 years). Our study highlights the need for psychosocial interventions to improve HIV treatment outcomes—particularly of adolescents and young adults—and supports strengthening mental health services in HIV treatment programmes.