This systematic review and meta-analysis examines the effectiveness of multisession psychosocial interventions compared with educational interventions and minimal interventions in reducing sexual risk in people who use drugs (51 studies; 19,209 participants). We conducted comprehensive searches (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and PsychINFO 1998-2012). Outcomes (unprotected sex, condom use, or a composite outcome) were extracted by two authors and synthesised using meta-analysis. Subgroup analyses and meta-regression were conducted to explore heterogeneity. Multisession psychosocial interventions had modest additional benefits compared to educational interventions (K = 46; OR 0.86; 95% CI 0.77, 0.96), and large positive effects compared to minimal interventions (K = 7; OR 0.60; 95% CI 0.46, 0.78). Comparison with previous meta-analyses suggested limited progress in recent years in developing more effective interventions. Multisession psychosocial and educational interventions provided similar modest sexual risk reduction justifying offering educational interventions in settings with limited exposure to sexual risk reduction interventions, messages, and resources.