Background: Users of opiates and stimulants are at sexual risk for HIV that can be reduced by psychosocial interventions. Objectives: We examined efficacy of 44 worldwide sexual risk reduction intervention studies with drug users (outcomes: unprotected sex, condom use, number of sex partners). We compared the results to our previous MA results (published in 2002) of 33 interventions conducted in the United States (US). The 44 interventions included the 33 interventions (published 1988 1999). Methods: We conducted comprehensive searches for sexual risk reduction intervention studies (experimental or quasi-experimental designs, 1988 August 2009). Effect sizes were converted to odds ratios (OR); an OR & 1.0 indicated less unsafe sexual behavior in experimental groups at follow-up. Results: Psychosocial interventions had modest additional benefit compared to shorter, control educational interventions (k = 44; OR, 0.87; 95% confidence interval [CI], 0.77 0.97), and larger positive effect compared to minimal interventions (k = 7; OR, 0.62; 95% CI, 0.47 0.83). Cumulative MA showed significant effect (OR = 0.88; 95% CI, 0.78 0.99) by 1996, similar to previous MA results. US (k = 38; OR, 0.87; 95% CI = 0.77 0.99) and non-US studies (k = 6; OR = 0.82; 95% CI = 0.63 1.06) had small effect, similar to previous MA results (k = 33; OR, 0.86; 95% CI = 0.76 0.98). Individual (k = 43; OR, 0.83; 95% CI, 0.73 0.94), network (k = 4, OR, 0.75; 95% CI, 0.47 1.18), and structural (k = 2; OR, 0.75; 95% CI, 0.60 0.94) interventions had similar effects; network and structural interventions seem promising. Meta-regression showed that HIV status (self-report or study test results; 0 20% vs. > 20%) was associated (B = 0.27, p = 0.04) with sexual risk reduction. Conclusion: Current and previous MA had similar results. Psychosocial interventions provide modest sexual risk reduction justifying offering them to drug users. Moderate-duration interventions may have diminishing returns. Stronger-effect interventions are needed.