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This study analyzed Iran’s national and subnational disease burden from 1990 to 2019 using data from the Global Burden of Disease Study 2019. Life expectancy increased to 79.6 years for women and 76.1 years for men, while the total DALYs remained relatively stable at 19.8 million, with a major shift toward non-communicable diseases. Although mortality and age-standardized DALY rates declined, disability-related burdens (YLDs) remained almost unchanged and now account for a larger share of DALYs. Regional inequalities in health outcomes narrowed over time, but deaths linked to risk factors rose despite overall declines in DALYs. The analysis found that international sanctions had a significant negative impact on health outcomes, particularly worsening mortality from non-communicable diseases.