Introduction <p>Deep brain stimulation (DBS) is a neuromodulatory intervention for severe, treatment-refractory obsessive-compulsive disorder (OCD). We conducted the first meta-analysis using individual participant outcome data, systematically evaluating (1) efficacy of DBS compared to sham-stimulation in randomized controlled trials (RCTs), (2) adverse events and (3) methodological trial quality.</p> Methods <p>We conducted a systematic search across multiple databases, including all RCTs comparing DBS with sham in adults with OCD, regardless of stimulation target. We obtained Yale-Brown Obsessive-Compulsive Scale (YBOCS) data for individual participants and performed a two-stage random-effects meta-analysis. We evaluated trial quality using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.</p> Results <p>Nine RCTs with small sample sizes were included, resulting in a total sample of 91 patients. Meta-analysis showed a decrease of 5.1 YBOCS points in favor of DBS compared to sham (95% confidence interval, CI, 2.0–8.1, 0.56 Hedges’ g). OR was 4.7, 95% CI 1.8–12.2), with a NNT of 3.9. Optimization strategy appeared to impact efficacy, in favor of trials using gradual adjustments of DBS parameters guiding towards maximal improvement (beta 5.1, 95% CI 0.59–9.5, p-value 0.026). Adverse events occurred during surgery, active- and sham trial phases, and follow-up, with hypomania and cognitive problems being the most frequently reported stimulation-related adverse events. GRADE quality of evidence was rated low.</p> Discussion <p>Concluding, we found a significant effect of DBS compared to sham in treating OCD. However, the quality of evidence was low, and heterogeneity was high. Additional, rigorous, sham-controlled evidence could further improve credibility of DBS for OCD.</p> PROSPERO-registration number <p>CRD42024546836</p>