To ascertain the potential contribution of serum lipids to the development of deep vein thrombosis (DVT), a case-control study was conducted in 143 DVT patients lacking thrombophilic risk factors and in 194 age- and sex-matched controls. DVT patients showed significantly higher body mass indices (BMI), and triglyceride levels than did controls (P < 0.001 and P = 0.045 respectively). Using multivariate analysis, BMI was the only variable which remained statistically different, thus the risk of DVT was associated with obesity (odds ratio = 2.49). These results were confirmed when additional control for fibrinogen and plasminogen activator inhibitor type 1 (PAI-1) was carried out in a subgroup of cases and controls. When idiopathic (n = 39) and secondary (n = 104) patients with DVT were compared, the former showed a higher mean age, a higher proportion of men, and higher cholesterol levels. Age, sex and total cholesterol were statistically different by multivariate analysis. After age was dichotomized as greater than or equal to 50 years and cholesterol greater than or equal to 5.69 mmol/l, all three variables constituted independent risk factors for idiopathic DVT, with odds ratios of 2.73 for ages greater than or equal to 50 years; 3.72 for men and 2.67 for cholesterolaemia greater than or equal to 5.69 mmol/l. Obesity thus constitutes an independent risk factor for DVT, possibly in part mediated through triglyceride, fibrinogen and PAI-1 effects on haemostasis. In addition, cholesterolaemia levels of greater than or equal to 5.69 mmol/l constitute an independent risk factor for idiopathic DVT.