Background <p>Rheumatic heart disease (RHD) is the most prevalent acquired heart condition among individuals under the age of 25, characterized by a significant risk of cardiac morbidity and mortality, which contributes to premature death. This study utilizes data from the Global Burden of Disease (GBD) 2021 to present an updated assessment of the burden of RHD at national and sub-national levels within Iran.</p> Methods <p>This study is a systematic analysis using data covering the years 1990 to 2021. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate (ASDR), and age-standardized disability-adjusted life years (DALYs) per 100,000 population for RHD in Iran and its 31 provinces were extracted from the GBD database for both sexes across age groups ranging from under 5 years to over 95 years. A temporal trend analysis and subnational assessment were conducted using DisMod-MR version 2.1.</p> Results <p>The ASPR and ASIR per 100,000 population remained relatively stable from 1990 to 2021. In contrast, the ASDR per 100,000 population experienced a significant decline, decreasing from 3.3 (95% uncertainty interval [UI]: 2.4 to 4.5) in 1990 to 1.4 (1.1 to 1.6) in 2021, corresponding to a reduction of 58.8% (-73.0 to -39.8). The ASDR per 100,000 population for women decreased by 57.5% (-78.0 to -32.8), while for men, it decreased by 59.9% (-75.0 to -34.7). Additionally, the age-standardized rate of DALYs per 100,000 population significantly decreased from 142.6 (111.9 to 181.2) in 1990 to 69.8 (55.7 to 88.5) in 2021, reflecting a reduction of 51.1% (-64.2 to -35.8). The reductions in age-standardized rates of DALYs per 100,000 population were 52.8% (-69.1 to -31.8) for women and 48.9% (-63.7 to -28.3) for men. Throughout the years from 1990 to 2021, women consistently exhibited higher ASPR, ASIR, age-standardized rates of DALYs, and ASDR per 100,000 population compared to men. The prevalence rates per 100,000 population of RHD were highest in the 30–34 age group, while the 15–19 age group exhibited the highest incidence rate per 100,000 population. The greatest rates of death and DALYs per 100,000 population were observed in individuals aged 95 years and older. Among the provinces, Qom, Zanjan, Semnan, Bushehr, and Yazd demonstrated the lowest overall burden of RHD, whereas Sistan and Baluchistan, Chahar Mahaal and Bakhtiari, and Tehran exhibited the highest burden.</p> Conclusion <p>The overall burden of RHD in Iran has decreased over the past three decades. However, this burden is not uniformly distributed across different sexes and age groups. Incidence and prevalence rates of RHD are notably higher among younger populations, whereas DALYs and deaths predominantly impact the elderly. Furthermore, women experience a greater burden of RHD compared to men. These findings emphasize the need for targeted healthcare policies to address resource allocation and interventions for RHD management, especially focusing on the vulnerable populations identified in this study.</p>