In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), body weight, height and body mass index (BMI) were evaluated as risk factors. Additionally, the joint effect of obesity together with oral contraceptive use and prothrombotic mutations on the risk of venous thrombosis were analysed. Three-thousand eight-hundred and thirty-four patients with a first venous thrombosis and 4683 control subjects were included, all non-pregnant and without active malignancies. Relative to those with a normal BMI (<25 kg/m2), overweight (BMI ≥ 25 and BMI < 30 kg/m2) increased the risk of venous thrombosis 1·7-fold [odds ratio (OR)adj(age and sex) 1·70, 95% confidence interval (CI) 1·55–1·87] and obesity (BMI ≥ 30 kg/m2) 2·4-fold (ORadj 2·44, 95% CI 2·15–2·78). An increase in body weight and body height also individually increased thrombotic risk. Obese women who used oral contraceptives had a 24-fold higher thrombotic risk (ORadj 23·78, 95% CI 13·35–42·34) than women with a normal BMI who did not use oral contraceptives. Relative to non-carriers of normal BMI, the joint effect of factor V Leiden and obesity led to a 7·9-fold increased risk (ORadj 7·86, 95% CI 4·70–13·15); for prothrombin 20210A this was a 6·6-fold increased risk (ORadj 6·58, 95% CI 2·31–18·69). Body height, weight and obesity increase the risk of venous thrombosis, especially obesity in women using oral contraceptives.