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Gallstone disease is one of the most prevalent digestive disorders globally, showing a trend toward increasing incidence and younger onset in Asian populations. Against this backdrop, this study aims to investigate the associations between 14 different obesity and lipid-related indices and gallstones, and to compare their predictive value for gallstone screening in the Chinese population. This study included 44,030 adult participants from the Beijing MJ Health Screening Center (2009–2023). Individuals with a history of cholecystectomy or gallstones at baseline were excluded. Gallstones were diagnosed via abdominal B-mode ultrasonography. Fourteen indices were calculated and evaluated, including BMI, WHtR, BRI, ABSI, LAP, VAI, CMI, CVAI, RFM, AIP, TyG, TyG-BMI, TyG-WC, and TyG-WHtR. Cox proportional hazards regression models were employed to assess the associations between these indices and gallstone risk, with stratified analyses performed by age (< 45 and ≥ 45 years) and sex. Restricted cubic splines (RCS) were used to evaluate non-linear relationships, and the performance and accuracy of prediction models were assessed using the C-index, calibration curves, Integrated Discrimination Improvement (IDI), and Net Reclassification Improvement (NRI). During the follow-up period, a total of 933 (2.12%) participants were diagnosed with new-onset gallstones. Multivariate-adjusted analyses revealed that, with the exception of ABSI, the remaining 13 indices were significantly and positively associated with gallstone risk. Stratified analysis uncovered significant population heterogeneity: CVAI demonstrated the optimal predictive ability in the young male, young female, and middle-aged/elderly male subgroups (C-indices: 0.611, 0.673, and 0.603, respectively), significantly outperforming other indices. Conversely, WHtR exhibited the best predictive performance in the middle-aged/elderly female subgroup (C-index: 0.589). Further validation indicated that the prediction model based on CVAI (for adult males and young females) possessed favorable discrimination and calibration, whereas the WHtR-based model (for middle-aged/elderly females) performed suboptimally. This study confirms that 13 obesity and lipid-related indices, excluding ABSI, are independent risk factors for gallstones in the Chinese population. The results support the implementation of a stratified risk assessment strategy: CVAI is identified as the preferred risk indicator for adult males and young females; for middle-aged and elderly females, WHtR may serve as a preliminary risk assessment tool to identify individuals who warrant further diagnostic evaluation. This study provides a scientific, convenient, and non-invasive assessment basis for the risk stratification and personalized intervention of gallstones in clinical practice.