Background: Urolithiasis is a common urological problem that is associated with high morbidity. A comprehensive assessment of the non-fatal and fatal health trends of urolithiasis by age, sex, and geography over time is necessary to inform policy to control this surgically managed non-communicable disease. Methods: This study was conducted using the standard GBD methodology and analytic tools. Cause-specific mortality rate (CSMR) was estimated using vital registration and verbal autopsy data and the Cause of Death Ensemble model (CODEm) modelling tool. CSMR estimates and incidence data from medical insurance claims and hospital discharges were analysed using a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to estimate age-, sex-, and location-specific incidence of urolithiasis between 2000 and 2021. Disability-adjusted life-years (DALYs) were the sum of years of life lost (YLL) and years lived with disability (YLDs). YLLs due to urolithiasis were calculated by multiplying the estimated number of deaths by the standard life expectancy at the age of death. YLDs were estimated by multiplying the disability weight by the symptomatic proportion of urolithiasis cases. The Global Burden of Diseases study used de-identified data, approved by the University of Washington IRB (Study Number 9060). Findings: There were 106 million (95% UI 88.3–129.0) incident cases of urolithiasis in 2021, of which 67% were in men (71.1 million [59.4–86.2)]). The global number of incident cases, deaths, and DALYs increased by 26.7% (23.8–29.8), 60.3% (41.5–84.7), and 34.5% (24.6–47.3), respectively, between 2000 and 2021. The global age-standardised incidence rate of urolithiasis experienced a significant decrease of 17.5% (14.7–20.0), while the age-standardised DALYs rate saw a reduction of 15.1% (6.8–21.3). Twelve GBD regions showed declining trends in the age-standardised incidence rate of urolithiasis between 2000 and 2021, and the remaining nine GBD regions had an increasing trend of age-standardised rates of urolithiasis. A significant increase in the age-standardised incidence rate of urolithiasis was observed in Central America, Tropical Latin America, and the Caribbean regions, whereas notable decline was observed in east Asia, eastern Europe, central Europe, and high-income North America. It was observed that the global age-standardised death rate was less than 0.5 per 100,000 across all GBD regions and less than 1 per 100,000 across all SDI quintiles, with fairly stable global age-standardised death rates of urolithiasis between 2000 and 2021. The age-standardised incidence rate of urolithiasis was 837 (688–1034) in low SDI regions and 1443 (12,108–1734) in high-middle SDI regions. Furthermore, the age-standardised DALY rate showed a decreasing trend across all SDI quintiles over the same period: high-middle SDI (−28.9% [–34.4 to −23.0]), middle SDI (−22.6% [–30.5 to −10.9]), and low-middle SDI (−2.9% [–15.8 to 12.9]). Interpretation: Global urolithiasis incidence and DALY rates have decreased, while the death rate has stabilised worldwide, showing significant variability among regions, SDI levels, and countries. This could be due to effective preventive measures c on urolithiasis risk factors, effective public health education, lifestyle changes, and early interventions and improved health care access at the global level. This analysis offers relevant insights into global, regional, and country-specific urolithiasis trends. Funding:Bill & Melinda Gates Foundation.