AbstractPrevious meta-analyses on psychotherapy for adult depression have found a larger treatment effect in non-Western trials compared to Western trials (i.e. North America, Europe, and Australia). However, factors contributing to this difference remain unclear. This study investigated different study characteristics between Western and non-Western trials and examined their association with effect size estimates. We systematically searched PubMed, PsycINFO, Embase, and Cochrane Library (01–09–2022). We included randomized-controlled trials (RCTs) that compared psychotherapy with a control condition. The validity of included RCTs was assessed by the Cochrane risk of bias assessment tool (RoB 1). Effect sizes were pooled using the random-effects model. Subgroup analyses and meta-regressions were also conducted. We identified 405 eligible trials, among which 105 trials (117 comparisons, 16 304 participants) were from non-Western countries. We confirmed that non-Western trials had a larger treatment effect (g = 1.10, 95% CI 0.90–1.31) than Western trials (g = 0.57, 95% CI 0.52–0.62). Trials from non-Western countries also had more usual care controls, higher risk of bias, larger sample sizes, lower mean ages, younger adults, more group-based interventions, and other recruitment methods (e.g. systematic screening; p < 0.05). The larger effect sizes found in non-Western trials were related to the presence of wait-list controls, high risk of bias, cognitive-behavioral therapy, and clinician-diagnosed depression (p < 0.05). The larger treatment effects observed in non-Western trials may result from the high heterogeneous study design and relatively low validity. Further research on long-term effects, adolescent groups, and individual-level data are still needed.