We explored the role of lipid accumulation products and visceral adiposity on the association between red meat consumption and markers of insulin resistance (IR) and inflammation in US adults. Data on red meat consumption, 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). Analysis of co-variance and “conceptus causal mediation” models were applied, while accounting for survey design. In adjusted models, a lower red meat consumption was significantly associated with a cardio-protective profile of IR and inflammation. Body mass index (BMI) had significant mediation effects on the associations between red meat consumption and C-reactive protein (CRP), Apolipoprotein-B, fasting glucose (FBG), insulin, homeostatic model assessment (HOMA) IR and β-cell function, glycated haemoglobin (HbA1c), triglyceride to high density lipoprotein (TG:HDL) ratio and triglyceride-glucose (TyG) index (all p < 0.05). Both waist circumference and anthropometrically predicted visceral adipose tissue (apVAT) mediated the association between red meat consumption with CRP, FBG, HbA1c, TG: HDL ratio and TyG index (all p < 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.