Some comorbidities, such as hypertension, are associated with higher von Willebrand factor ( VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease ( VWD). Therefore, we studied this association in patients with type 1 ( n = 333) and type 2 ( n = 203) VWD from the ‘WiN” study. VWF antigen ( VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0·23 iu/ml, 95% confidence interval ( CI): 0·11–0·35], diabetes mellitus (0·11 iu/ml, 95% CI: −0·02 to 0·23), cancer (0·14 iu/ml, 95% CI: 0·03–0·25) and thyroid dysfunction (0·14 iu/ml, 95% CI: 0·03–0·26) than in patients without these comorbidities (all corrected for age, sex and blood group). Similar results were observed for VWF collagen binding capacity ( VWF: CB), VWF activity as measured by the VWF monoclonal antibody assay ( VWF:Ab) and factor VIII ( FVIII) coagulant activity ( FVIII:C). In type 1 VWD, age was associated with higher VWF:Ag (0·03 iu/ml; 95% CI: 0·01–0·04), VWF: CB (0·02 iu/ml; 95% CI: 0·00–0·04), VWF:Ab (0·04 iu/ml; 95% CI: 0·02–0·06) and FVIII:C (0·03 iu/ml; 95% CI: 0·01–0·06) per decade increase. After adjustment for relevant comorbidities, these associations were no longer significant. Despite the higher VWF and FVIII levels, type 1 VWD patients with comorbidities had more bleeding episodes, particularly during surgery. There was no association between comorbidities and VWF/ FVIII levels or bleeding phenotype in type 2 VWD patients. In conclusion, comorbidities are associated with higher VWF and FVIII levels in type 1 VWD and may explain the age‐related increase of VWF and FVIII levels.