Purpose <p>Urolithiasis is a common, recurrent condition that poses significant health and economic challenges. This study aims to assess the global, regional, and national trends in urolithiasis burden and explore its association with socio-demographic disparities from 1992 to 2021.</p> Methods <p>We utilized data from the Global Burden of Disease (GBD) 2021 to analyze the burden of urolithiasis across 204 countries and territories from 1992 to 2021. Age-standardized incidence rates (ASIR), DALY rates (AS-DALYR), and years of life lost rates (ASYR) were assessed. Inequality analysis was performed to evaluate socio-demographic disparities. Age-period-cohort (APC) analysis examined trends by age, period, and cohort.</p> Results <p>In 2021, urolithiasis was responsible for 693,444 DALYs globally, with an AS-DALYR of 8.146 per 100,000 and 105,984,000 cases (ASIR: 1242.840). Despite a moderate global decline (AAPC: -0.159), males exhibited a higher burden, with 412,237 DALYs (AS-DALYR: 10.092) and an ASIR of 1685.100. Asia and Europe accounted for the highest burdens, while Oceania had the lowest. Regional disparities persisted, particularly in Europe and Oceania. APC analysis showed increasing age-specific risks in older populations, particularly in Americas and Europe. Limitations include data accuracy, bias of statistical models and limited consideration of risk factors.</p> Conclusion <p>This study highlights persistent global inequalities in the urolithiasis burden, with marked regional and gender disparities. The burden remains particularly high in Asia and Europe, with increasing trends observed in Americas. Targeted interventions are urgently required, focusing on high-risk groups such as males, older adults, and specific birth cohorts.</p> Trial registration <p>Not applicable.</p>