Both gallstone disease and sleep disorders are important public health problems. Few studies to date have investigated the associations between sleep and gallstone disease in humans. This study aimed to assess whether sleep factors (sleep time, sleep amounts, trouble sleeping) were associated with gallstone disease in the United States adults.This was a population-based cross-sectional study of US adults, which included data of participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES) gathered between 2017 and March 2020. The assessment of gallstone disease and sleep factors was based on self-reported data. We used sample-weighted logistic regression and restricted cubic spline models to explore the associations between sleep factors and gallstone disease. Subgroup analyses were conducted to assess the interaction between trouble sleeping and interacting factors.The prevalence of gallstone disease was 11% among the 9,210 adult participants. Going to bed late on weekdays (OR, 1.41; 95% CI, 1.15 to 1.74) and weekends (OR, 1.43; 95% CI, 1.14 to 1.78), and short sleep duration on weekdays (OR, 1.29; 95% CI, 1.00 to 1.68) were factors associated with increased risk of gallstone disease, and we detected dose-response associations with the restricted cubic spline model (RCS) models, after adjusting for confounders. Presenting trouble sleeping was associated with increased risk of gallstone disease (OR, 1.52; 95% CI, 1.03 to 2.23) and the association was influenced by the presence of thyroid disease (P for interaction = 0.037).Our study results indicate that going to bed late, short sleep duration, and trouble sleeping were associated with increased risk of gallstone disease in a nationally representative sample of adults in the US.© 2024. The Author(s).