We examined the efficacy of psychological adherence-enhancing interventions (AEIs) compared with usual care in HIV-infected adults under antiretroviral treatment (ART) by focusing on adherence and clinical HIV markers as outcomes in the short term and long term. We searched relevant databases for controlled studies that compared psychological AEIs with usual care. We included 31 comparisons from 27 individual studies in our meta-analyses. Psychological AEIs were significantly superior to usual care in improving adherence [standardized mean difference (SMD) 0.30, 95% CI 0.20-0.40] and reducing HIV viral load (SMD 0.15, 0.07-0.23) at the end of treatment. At the last follow-up, we found no difference between psychological AEIs and usual care, neither on adherence (SMD 0.07, -0.11-0.24) nor on clinical markers (SMD 0.06, -0.03-0.15). After excluding outliers from the analyses, between-study heterogeneity was small, and we did not identify any relevant moderators of intervention effects. In summary, psychological AEIs may significantly improve ART adherence and HIV viral load compared with usual care in the short term, but fail to be superior in achieving long-lasting improvements on ART adherence and clinical HIV markers as compared with usual care. Owing to limited quality and the majority of studies being conducted in the United States or Europe, our results have to be interpreted with caution, and are most relevant to the United States and Europe. The consistently reported difficulties to achieve sustained ART adherence improvements in previous and the present meta-analyses highlight the need to focus on maintaining ART adherence improvements in future research.