<p>Urolithiasis is a common condition worldwide, marked by significant variations in lifetime risk across different regions, genders, and socioeconomic backgrounds. Understanding these disparities is crucial for developing effective public health strategies. This study aims to analyze these risks from 1990 to 2021 and project future trends in the incidence and mortality of urolithiasis. Data were obtained from the Global Burden of Disease (GBD) 2021 study, which provides comprehensive estimates on urolithiasis incidence, prevalence, and mortality across various demographics. Analyses were stratified by gender, age, Sociodemographic Index (SDI), and geographic regions, and included assessments of temporal trends and concentration indices (CIs). Additionally, AutoRegressive Integrated Moving Average (ARIMA) models were employed to project future trends regarding the lifetime risk of developing urolithiasis.The global lifetime risk of developing urolithiasis in 2021 was estimated at 62.95%, with the highest risks observed in Eastern Europe (89.20%), Southern Latin America (80.34%), and Central Asia (75.75%). Men exhibited a higher risk than women (70.40% vs. 50.34%). The global mortality risk from urolithiasis remained low at 0.03%, with the highest rates found in High-income Asia Pacific (0.07%) and Eastern Europe (0.06%). Notably, the lifetime risk of developing urolithiasis declined with advancing age, particularly after 40. ARIMA projections suggest a moderate increase in lifetime risk, potentially reaching nearly 70% by 2050, especially among females. Urolithiasis demonstrates significant global and regional disparities influenced by socioeconomic, environmental, and demographic factors. Comprehensive strategies that address these disparities will be essential for enhancing public health outcomes and reducing the incidence of urolithiasis worldwide.</p>