Because the relationship between factor XII deficiency and venous thrombosis is unclear and study results seem contradictory, we undertook a population-based case-control study. Among 350 unselected patients younger than 70 years, with a first, objectively confirmed, episode of deep-vein thrombosis and without underlying malignant disease we detected a 6% frequency (21/350 patients) of factor XII deficiency (activity level < 57%). Among 350 healthy control subjects, matched for age and sex, the frequency was 5% (18 subjects). Thus there is no increase in prevalence of factor XII deficiency among thrombosis patients and no increase in thrombosis risk for subjects with low factor XII levels (matched odds ratio 1.2 (95% CI 0.6-2.4)). In addition, there was no relation between strata of factor XII levels and thrombosis risk. In conclusion, we do not consider factor XII to be a determinant of deep-vein thrombosis.