•Age-dependent effects on plasma VWF levels in type 1 VWD define distinct subgroups with important differences in underlying pathogenesis.•Low VWF does not constitute a discrete clinical-pathological entity; rather, it is part of an age-dependent type 1 VWD evolving phenotype. Display omitted There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained <30 IU/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU/dL) in 30% and normalized (>50 IU/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (β = 0.00; 95% confidence interval, −0.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity/VWF:Ag or VWF propeptide/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria. von Willebrand disease (VWD) is the most common inherited bleeding disorder, but diagnosis and accurate subtyping of VWD are complex and have been controversial. Atiq et al analyzed data from 2 large cohort studies to illuminate the natural history of patients with reduced (30-50 IU/dL) von Willebrand factor (VWF) who did not meet the strict definition of type 1 VWD (VWF levels <30 IU/dL). The authors’ data support the hypothesis that low VWF is an age-dependent evolution of type 1 VWD rather than its own discrete clinical entity. This finding reinforces the general principle that bleeding phenotype should be the key determinant of management decisions in patients with VWD.