Shared risk factors help explain the association between venous thromboembolism (VTE) and atherothrombosis. The potential association between insulin resistance and VTE has been poorly evaluated. Thus, we aimed to assess the association between insulin resistance and VTE in the EDITH hospital-based case-control study. Between May 2000 and December 2004, 677 patients with unprovoked VTE and their age- and sex-matched controls were included. Fasting glycaemia and insulinaemia were measured and insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR) equation. The association between HOMA-IR and VTE was determined in non-diabetic patients in a quintile-based analysis. A total of 590 non-diabetic cases (median age 73.0 years, 255 men) and 581 non-diabetic controls (median age 72.0 years, 247 men) were analysed. There was a trend for a higher median level of HOMA-IR index in cases than in controls (1.21 [interquartile range 0.84-2.10] vs1.19 [interquartile range 0.72-2.02], p=0.08). The unadjusted analysis showed an increased risk of unprovoked VTE associated with increasing HOMA-IR (odds ratio [OR] 1.53; 95% confidence interval [CI] 1.00-2.34 for the highest quintile of HOMA-IR compared with the first quintile). Adjustment for lipid lowering drugs and antiplatelet agents use slightly modified the association (OR 1.51; 95% CI 0.97-2.34). When body mass index was added in the adjusted model, HOMA-IR was no longer associated with VTE (OR 1.08; 95% CI 0.67-1.73). Our results highlight the role of body mass index in the association between cardiovascular risk factors and VTE.