Self-injurious thoughts and behaviors (SITBs) are major public health concerns impacting a wide range of individuals and communities. Despite major efforts to develop and refine treatments to reduce SITBs, the efficacy of SITB interventions remains unclear. To provide a comprehensive summary of SITB treatment efficacy, we conducted a meta-analysis of published randomized controlled trials (RCTs) that have attempted to reduce SITBs. A total of 591 published articles from 1,125 unique RCTs with 3,458 effect sizes from the past 50 years were included. The random-effects meta-analysis yielded surprising findings: The overall intervention effects were small across all SITB outcomes; despite a near-exponential increase in the number of RCTs across five decades, intervention efficacy has not improved; all SITB interventions produced similarly small effects, and no intervention appeared significantly and consistently stronger than others; the overall small intervention effects were largely maintained at follow-up assessments; efficacy was similar across age groups, though effects were slightly weaker for child/adolescent populations and few studies focused on older adults; and major sample and study characteristics (e.g., control group type, treatment target, sample size, intervention length) did not consistently moderate treatment efficacy. This meta-analysis suggests that fundamental changes are needed to facilitate progress in SITB intervention efficacy. In particular, powerful interventions target the necessary causes of pathology, but little is known about SITB causes (vs. SITB correlates and risk factors). The field would accordingly benefit from the prioritization of research that aims to identify and target common necessary causes of SITBs. (PsycInfo Database Record (c) 2020 APA, all rights reserved).