We explored the role of lipid accumulation products and visceral adiposity on the association between red meat consumption (RMC) and markers of insulin resistance (IR) and inflammation in USA adults. Data on RMC and health outcome measurements were extracted from the 2005–2010 US National Health and Nutrition Examination Surveys. Overall 16 621 participants were included in the analysis (mean age = 47·1 years, 48·3 % men). ANCOVA and ‘conceptus causal mediation’ models were applied while accounting for survey design. In adjusted models, a lower RMC was significantly associated with a cardio-protective profile of IR and inflammation. BMI had significant mediation effects on the association between RMC and C-reactive protein (CRP), apo B, fasting blood glucose (FBG), insulin, homoeostatic model assessment of IR and β-cell function, glycated Hb (HbA1c), TAG:HDL ratio and TAG glucose (TyG) index (all Ps < 0·05). Both waist circumference and anthropometrically predicted visceral adipose tissue mediated the association between RMC and CRP, FBG, HbA1c, TAG:HDL ratio and TyG index (all Ps < 0·05). Our findings suggest that adiposity, particularly the accumulation of abdominal fat, accounts for a significant proportion of the associations between red meat consumption, IR and inflammation.