To investigate the association of triglycerides/glucose index (TyG index), anthropometrically predicted visceral adipose tissue (apVAT), lipid accumulation product (LAP), visceral adiposity index (VAI) and triglycerides (TG):high density lipoprotein-cholesterol (HDL-C) ratio with insulin resistance (IR) in adult Americans. This study was based on data from three NHANES cycles (2005 to 2010). The TyG index was calculated as ln TG×fasting glucose/2. VAI was calculated using gender-specific formulas: men waist circumference (WC)/39.68+(1.88×body mass index (BMI)×(TG/1.03)×(1.31/HDL-C); women: WC/36.58+(1.89×BMI)×(TG/0.81)×(1.52/HDL-C). LAP index was calculated as WC–65×TG in men, and WC–58×TG in women. Correlation and regression analyses accounted for the complex sampling of database. A total of 18,318 subjects was included in this analysis mean age 47.6Years; 48.7% (n=8918) men. The homeostatic model assessment of insulin resistance (HOMA-IR) had a significant positive correlation with the TyG index (r=0.502), LAP (r=0.551), apVAT (r=0.454), TG:HDL-C ratio (r=0.441) and VAI (r=451) (p<0.001 for all comparisons). Bland-Altman plots showed no systematic errors. The optimal cut-off to predict HOMA-diagnosed IR was 0.473 (sensitivity=74.5% and specificity=72.7%) for LAP, 0.478 (75.9%, 71.9%) for TyG, 0.391 (70.4%, 67.1%) for VAI, 0.392 (77.1% and 62.0%) for TG:HDL-C ratio and 0.381 (63.8%, 74.8%) for apVAT. The LAP index is a simple, cheap and accurate although not perfect, surrogate marker of HOMA-diagnosed IR among adult Americans. Moreover, it has higher predictability than other screening tools which traditionally applied. Among the markers, apVAT had the highest specificity and the TG:HDL-C ratio had the highest sensitivity.