Abstract: Objective To analyze the association between relative fat mass index (RFM) and the risk of gallstones in adults. Methods Adult participants from the National Health and Nutrition Examination Survey (NHANES) were included. RFM was calculated based on the participants' height and waist circumference. The history of gallstone disease was obtained through self-reports. The relationship between RFM and the risk of gallstones was assessed using Logistic regression analysis, smooth curve fitting and subgroup analysis. Results A total of 4, 874 participants were included in the study. The RFM level of gallstone subjects was significantly higher than that of non-gallstone subjects (P<0.001). After adjusting for various confounders, RFM level was found to be independently associated with the risk of gallstones (OR=1.095, 95%CI: 1.022 to 1.173, P=0.010). Smooth curve fitting analysis indicated that the risk of gallstone disease also increased as RFM levels increased. The results of subgroup analysis showed no significant differences in the relationship between RFM and gallstones across different populations. Conclusion Higher RFM level is associated with an increased risk of gallstones in participants. RFM may serve as an economical, effective and convenient indicator for assessing the risk of gallstones, but further prospective studies are required to validate these findings.