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Purpose: To assess cost-effectiveness of sclerotherapy for venous malformations (VMs) to improve patient quality of life (QOL)., Materials and Methods: This prospective study enrolled 28 patients with symptomatic VMs who underwent sclerotherapy. EuroQol-5 Dimension (EQ-5D) and Short-Form 36 (SF-36) Health Survey were used to measure health-related QOL. Questionnaires were collected before and 1, 3, 6, and 12 months after sclerotherapy. Quality-adjusted life years (QALYs) were calculated using EQ-5D score as a measure of health utility. Medical costs obtained from the hospital accounting system and other costs of staff, drugs, materials, and angiographic equipment were calculated for each procedure. Cost-effectiveness was analyzed using incremental cost-effectiveness ratio (ICER) as the medical cost/gain of QALYs., Results: Median EQ-5D scores improved from 0.768 (range, 0.705-1) to 1 (range, 0.768-1) after 6 months (P = .023) and 1 (range, 0.768-1) after 12 months (P = .063). The gain of QALYs at 12 months was 0.043. The mean medical cost was ¥281,228 ($2,337). The pain group (baseline bodily pain scale of SF-36 score < 70) showed greater improvement in median EQ-5D score, from 0.705 (range, 0.661-0.768) to 0.768 (range, 0.705-1) after 6 months (P = .041) and 0.768 (range, 0.768-1) after 12 months (P = .049). ICER at 12 months was ¥6,600,483 ($54,840) in the overall group and decreased to ¥3,998,113 ($33,218) in the pain group, < ¥6,000,000 ($49,850), threshold for acceptance of a public health benefit in Japan, even accounting for 50% increase in costs., Conclusions: Sclerotherapy was cost-effective for improving QOL for symptomatic VMs, especially for patients with moderate to severe pain., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)