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von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life.This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate or severe VWD, and assessed whether bleeding severity and type of VWD are associated with HR-QoL.HR-QoL was assessed using the Short Form (SF)-36, and bleeding severity was measured using the Bleeding Score (BS).Five hundred and nine patients participated; 192 males and 317 females, median age and range 45 (16–87) and 47 (16–84) years, respectively. Compared with the general population, HR-QoL in VWD patients was lower in the vitality domain (61 vs. 66 P < 0.001 for females, 67 vs. 72 P < 0.001 for males). Patients with the most severe bleeding phenotype (highest quartile BS, BS > 17) had a lower HR-QoL in eight domains than patients with a less severe bleeding type (lowest quartile BS, BS < 7) in the univariate analysis. After adjustment for age, gender, co-morbidity and employment/educational status, a more severe bleeding phenotype was associated with lower scores on the domains of physical functioning, role limitations due to physical functioning, bodily pain, general health, social functioning and physical component summary.HR-QoL is lower in VWD patients compared with the general population. HR-QoL is strongly associated with bleeding phenotype.