Gallstones is common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21st century.We systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between Jan 1, 2000 and Nov 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity.Based on 115 studies with 32,610,568 participants, pooled prevalence of gallstones was 6.1% (95% CI, 5.6-6.5) Prevalence was higher in females vs. males (7.6% vs. 5.4%), in South America vs. Asia (11.2% vs. 5.1%), in upper-middle income country vs. high-income country (8.9% vs. 4.0%) and with advancing age. On sensitivity analysis of population-based studies, prevalence of gallstones was 5.5% (95% CI, 4.1-7.4; n=44 studies), and on limiting to imaging-based detection modalities, prevalence was 6.7% (95% CI, 6.1-7.3; n=101 studies). Prevalence was stable over the last 20 years. Based on 12 studies, incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37-0.51), without differences between males and females, and with rising incidence in more recent studies.Globally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be rising. Our findings call for prioritizing research on prevention of gallstones.Copyright © 2024. Published by Elsevier Inc.