Abstract Gallstones (GS) are closely associated with obesity. The body mass index (BMI) is the most commonly used index for evaluating obesity. However, BMI does not consider the distribution of adipose tissue and does not differentiate between differences in fat distribution by sex; therefore, BMI only provides a rough indication of overweight status. Relative fat mass (RFM) is an emerging, simple, and low-cost anthropometric index that reflects obesity (particularly abdominal obesity), and is associated with various obesity-related diseases. However, the relationship between the RFM and GS has not yet been explored. Therefore, this study aimed to evaluate the relationship between RFM and the risk of developing GS, the age of patients at the time of their first GS surgery, and to evaluate the predictive value of RFM for the risk of developing GS. Data from the National Health and Nutrition Examination Survey (2017–2020) were used. Logistic regression and dose-response curves were used to analyze the relationship between RFM levels and the prevalence of GS. Multiple linear regression and dose-response curves were used to analyze the relationship between RFM levels and patient age at the time of the first GS surgery. Subgroup analyses further explored the relationship between RFM and age, sex, race, hypertension, and diabetes mellitus. Receiver operating characteristic (ROC) curves were used to analyze the predictive ability of RFM for GS development. Overall, 7978 adults aged ≥ 20 years were included in this study, of whom 828 had a history of GS. After adjusting for potential confounders, each 1-unit increase in RFM was associated with a 9% increase in GS prevalence (odds ratio: 1.09, 95% confidence interval : 1.07, 1.11), with dose-response curves confirming a positive, nonlinear correlation. And the threshold for the effect of RFM on the prevalence of GS was 40.99. Subgroup analyses revealed that the positive correlation between RFM and GS prevalence remained stable in all populations despite subtle differences. The results of the ROC curves suggested that the predictive value of RFM for GS prevalence was superior to that of BMI. In addition, dose-response curves revealed a nonlinear relationship between RFM and patient age at the time of the first GS surgery, and the threshold for the effect of RFM on age at the first GS surgery was 30.99. RFM is closely associated with GS, and in general, higher levels of RFM are associated with a higher risk of GS. RFM is a better predictor of the risk of GS than BMI. Due to the nature of this cross-sectional study, we were unable to determine a causal relationship between the two.