Overproduction of vascular endothelial growth factor (VEGF) seems to contribute to the pathogenesis, still unclear, of POEMS Syndrome. Our study retrospectively reviewed the clinical and VEGF data from a multicenter Italian cohort of patients affected by POEMS syndrome who underwent to autologous peripheral blood stem cell transplantation (aPBSCT) in order to find an impact on clinical improvement or outcome. Patients with VEGF levels higher than 758 pg/mL were at higher risk of relapse, with sensible difference in PFS (p = 0.007). VEGF could be used as a marker of relapse and as a marker of disease intensity in patients with POEMS.