Background: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. Objectives: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. Methods: Fifty-one obese (body mass index [BMI] >= 30 kg m(-2)) and 47 non-obese (BMI <= 25 kg m(-2)) hemophilia A patients, and 42 obese and 50 matched non-obese male controls were included. Carotid and femoral intimamedia thickness [IMT] and brachial flow-mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. Results: The overall population age was 50 +/- 13 years. Carotid IMT was increased in obese subjects (0.77 +/- 0.22 mm) as compared with non-obese subjects (0.69 +/- 0.16 mm) [mean difference 0.07 mm (95% confidence interval [CI] 0.02-0.13, P = 0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02 mm [95% CI - 0.07-0.11, P = 0.67], and mean difference of 0.06 mm [95% CI - 0.13-0.25, P = 0.55], respectively). Thirty-five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P = 0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84% +/- 3.24% and 5.32% +/- 2.37%, P = 0.45). Conclusion: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary.