The aim of this study was to assess Health-Related Quality of Life (HRQoL) in a population of patients with vascular malformations outside the central nervous system (CNS) and to compare the results with data from a national reference population.In total, 111 consecutive patients above 14 years of age and referred for the first time to the national vascular malformation center from September 2011 to December 2012 were included. HRQoL was assessed using the Short-Form 36-item questionnaire (SF-36), which is a validated questionnaire with eight domains, covering both physical and mental aspects of HRQoL. The results were compared with national reference values. Possible association between HRQoL and selected demographic and clinical variables was analyzed using linear regression analysis.The sample consisted of 47 men (42.3%) and 64 women (57.7%). The median age of patients was 27 years (range 14-63 years). Ninety-six patients (86.5%) were diagnosed with venous malformations and nine patients (8.1%) with arteriovenous malformations. Six patients had other types of malformations (9%). The patients had significantly lower SF-36 scores in all domains, except for General health, than the general population. There was a significant association between muscular involvement and lower SF-36 scores in the physical domains Bodily pain and Role limitation due to physical problems.Our data suggest that patients with vascular malformations outside the CNS have impaired quality of life when compared with the general population. Muscular involvement seems to be associated with worse HRQoL in the physical aspects.