Background: Coffee consumption is associated with a lower risk of venous thrombosis, but the role of confounding and the pathophysiology behind these findings are unclear. Objective: To assess the role of haemostatic factors in the relation between coffee consumption and venous thrombosis. Methods: From a large case-control study, 1803 patients with a first venous thrombosis and 1803 partner controls were included. With conditional logistic regression, odds ratios (OR) and 95% confidence intervals for venous thrombosis were calculated for coffee consumption versus no coffee consumption. In addition, mean differences in haemostatic factor levels between these groups were calculated in the controls. Results: Coffee consumption yielded a 30% lower risk of venous thrombosis compared with no coffee consumption (OR 0.7, 0.5-0.9). Adjustment for several putative confounders (age, sex, BMI, smoking, hormonal factors, statin, aspirin, alcohol, malignancy and chronic disease) yielded an OR of 0.8 (0.6-1.1). Results were similar for provoked and unprovoked events, and for deep vein thrombosis and pulmonary embolism. In controls, von Willebrand factor was 11 (3 to 19) IU/dL lower and factor VIII levels were 11 (1 to 21) IU/dL lower in coffee consumers than in non consumers. After adjusting the risk estimates for these haemostatic factors, the inverse association between coffee consumption and venous thrombosis diminished: OR 1.0 (0.7-1.4). There was no association between coffee consumption and anticoagulant proteins, fibrinogen levels or fibrinolytic markers. Conclusions: Coffee consumption is associated with a lower risk of venous thrombosis, which seems to be mediated through von Willebrand factor and factor VIII. © 2012 International Society on Thrombosis and Haemostasis.