Abstract Purpose The aim of this study is to investigate drug use disorders which are a major cause of Disability Adjusted Life Years (DALYs) in the Eastern Mediterranean Region (EMR). Methods This article is a part of the global burden of diseases (GBD), injuries, and risk factors 2019 study. The GBD modeling approach was used to estimate population-level prevalence of drug use disorders. We combined these estimates with disability weights to calculate years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 1990–2019. Results It is estimated that in 2019 in EMR around 3.4 million people have drug use disorder which has increased by 137% compared to 1990. Also, in 2019, DALY number for drug use disorders was 1217.9 (95% UI: 940.4, 1528.9) thousand years and 7645 (95% UI: 6793.7, 8567.9) deaths occurred. The DALY rate increased 39.6% in the region since1990, whereas the global rate increased by 24.4%. United Arab Emirates, Libya, and Iran were most affected by drug use disorders with the highest rates of age-standardized DALY in EMR in 2019. The most prevalent drug use disorder in the region is opioid use which is accountable for 80% of all drug use disorders DALYs. Conclusion Despite many interventions, drug use disorders are still responsible for high rates of DALY in the region which has increased since 1990 in both males and females; more comprehensive policies, better control measures and proper education could reduce the adverse effects.