Introduction: During the last decade, thermal ablation techniques such as endovenous laser ablation have been challenging the position of traditional surgery for the treatment of saphenous varicose veins. The newest method of thermal ablation is pulsated steam, which works by heating the vein with steam at 120 degrees C. This study assessed the effectiveness of steam ablation of varicose veins in sheep and in humans. Methods: The safety of the procedure in sheep was assessed by cardiovascular monitoring during treatment. We used ultrasound imaging to examine occlusion of the veins. Changes in treated veins were examined microscopically. In a pilot study, 20 veins in 19 patients with insufficiency of the great or the small saphenous vein were treated with pulsated steam ablation. Anatomic success, patient satisfaction, and complications were investigated for 6 months after the procedure. Results: All veins in the sheep were occluded. No cardiovascular changes occurred during treatment. Histologic examination of treated veins showed typical changes of the vein wall, such as disappearance of the endothelial layer, fibrotic thrombosis, and major alterations in collagen fibers in the media. Steam ablation was effective in the 19 patients: 13 of 20 veins were completely closed, and 7 showed a very small segment of recanalization after 6 months of follow-up that did not seem to be clinically relevant. Nine patients had some ecchymoses at the puncture site, and one patient had a transient superficial phlebitis. A median maximal pain score of 1 (range, 0-10) was reported. No serious side effects, such as deep vein thrombosis, nerve injury, skin burns, or infections, were reported. Patients were very satisfied with the treatment, with a median satisfaction score of 9.25 (range, 0-10). Conclusions: In this proof-of-principle study, pulsated steam ablation was an effective treatment for saphenous varicose veins. (J Vasc Surg 2011;53:181-6.) Clinical Relevance: This article describes a proof-of-principle study on the newest thermal endovascular treatment, steam ablation. It describes the first group of patients treated with hyperheated steam of 120 degrees C for ablation of saphenous varicose veins. It also reports basic experimental data of this treatment on sheep to investigate the safety profile and the morphologic and histologic changes resulting from steam ablation. Steam ablation in the patients was effective, safe, and very well appreciated by the patients. This article describes the steam ablation procedure in humans, shows the first results, and provides basic background information received from animal experiments.