The physical benefits of resistance exercise training (RET) are well documented, but less is known regarding the association of RET with mental health outcomes. To date, no quantitative synthesis of the antidepressant effects of RET has been conducted. To estimate the association of efficacy of RET with depressive symptoms and determine the extent to which logical, theoretical, and/or prior empirical variables are associated with depressive symptoms and whether the association of efficacy of RET with depressive symptoms accounts for variability in the overall effect size. Articles published before August 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Randomized clinical trials included randomization to RET (n = 947) or a nonactive control condition (n = 930). Hedges d effect sizes were computed and random-effects models were used for all analyses. Meta-regression was conducted to quantify the potential moderating influence of participant and trial characteristics. Randomized clinical trials used validated measures of depressive symptoms assessed at baseline and midintervention and/or postintervention. Four primary moderators were selected a priori to provide focused research hypotheses about variation in effect size: total volume of prescribed RET, whether participants were healthy or physically or mentally ill, whether or not allocation and/or assessment were blinded, and whether or not the RET intervention resulted in a significant improvement in strength. Fifty-four effects were derived from 33 randomized clinical trials involving 1877 participants. Resistance exercise training was associated with a significant reduction in depressive symptoms with a moderate-sized mean effect ∆ of 0.66 (95% CI, 0.48-0.83; z = 7.35; P < .001). Significant heterogeneity was indicated (total Q = 216.92, df = 53; P < .001; I2 = 76.0% [95% CI, 72.7%-79.0%]), and sampling error accounted for 32.9% of observed variance. The number needed to treat was 4. Total volume of prescribed RET, participant health status, and strength improvements were not significantly associated with the antidepressant effect of RET. However, smaller reductions in depressive symptoms were derived from randomized clinical trials with blinded allocation and/or assessment. Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed.