Aims To estimate the prevalence and burden of disease attributable to opioid dependence globally, regionally and at country level. Methods Multiple search strategies: (i) peer‐reviewed literature searches; (ii) systematic searches of online databases; (iii) internet searches; (iv) consultation and feedback from experts. Culling and data extraction followed protocols. DisMod‐MR, the latest version of the generic disease modelling system, a Bayesian meta‐regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. Disability weight for opioid dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs). Opioid dependence premature mortality was computed as years of life lost (YLLs) and summed with YLDs to calculate disability‐adjusted life years (DALYs). Results There were 15.5 million opioid‐dependent people globally in 2010 [0.22%, 95% uncertainty interval (UI) = 0.20–0.25%]. Age‐standardized prevalence was higher in males (0.30%, 95% UI = 0.27–0.35%) than females (0.14%, 95% UI = 0.12–0.16%), and peaked at 25–29 years. Prevalence was higher than the global pooled prevalence in Australasia (0.46%, 95% UI = 0.41–0.53%), western Europe (0.35%, 95% UI = 0.32–0.39) and North America (0.30%, 95% UI = 0.25–0.36). Opioid dependence was estimated to account for 9.2 million DALYs globally (0.37% of global DALYs) in 2010, a 73% increase on DALYs estimated in 1990. Regions with the highest opioid dependence DALY rates were North America (292.1 per 100 000), eastern Europe (288.4 per 100 000), Australasia (278.6 per 100 000) and southern sub‐Saharan Africa (263.5 per 100 000). The contribution of YLLs to opioid dependence burden was particularly high in North America, eastern Europe and southern sub‐Saharan Africa. Conclusion Opioid dependence is a substantial contributor to the global disease burden; its contribution to premature mortality (relative to prevalence) varies geographically, with North America, eastern Europe and southern sub‐Saharan Africa most strongly affected.