Background Cholecystectomy, central obesity, and insulin resistance (IR) are established risk factors for nonalcoholic fatty liver disease (NAFLD). We aimed to examine the relative contributions and combined association of cholecystectomy and central obesity/IR with NAFLD risk. Methods We conducted a cross-sectional analysis of data from the third National Health and Nutrition Examination Survey (NHANES III), in which ultrasonography was performed. Odds ratios (ORs) and 95% confidence intervals for NAFLD were estimated using logistic regression. Results Cholecystectomy associated with a higher prevalence of NAFLD compared with gallstones among both centrally obese and non-centrally-obese subjects. Gallstones associated with a higher prevalence of NAFLD only in the presence of central obesity. In centrally obese participants, the OR increased from 2.67 (2.15-3.32) for participants without gallstone disease to 6.73 (4.40-10.29) for participants with cholecystectomy. In participants with cholecystectomy, the OR increased from 2.57 (1.35-4.89) for participants without central obesity to 6.73 (4.40-10.29) for centrally obese counterparts. We observed a modest increase in the risk of NAFLD with cholecystectomy compared with a large increase in the risk with IR or metabolic syndrome. Conclusion The magnitude of the NAFLD risk contributed by cholecystectomy was similar to central obesity in combined analyses. The magnitude of the association with IR or metabolic syndrome was greater than with cholecystectomy.