In foam sclerotherapy for varicose veins, ultrasound can track the spread of foam in only one direction. We hypothesized that using fluoroscopy in combination with ultrasound can reveal the spread of foam to deep veins through perforator veins and to other varicose veins in different directions. In this study, we examined the safety and effectiveness of ultrasound- and fluoroscopy-guided foam sclerotherapy for lower extremity venous ulcers. This retrospective study included all patients receiving ultrasound- and fluoroscopy-guided foam sclerotherapy for varicose ulcers (Clinical, Etiology, Anatomy, and Pathophysiology class 6) of the lower extremities at the Fourth Affiliated Hospital of Jiangsu University (Zhenjiang, China) between May 1, 2016, and April 30, 2018. Polidocanol foam sclerosant was injected through indwelling needles (placed every 20 cm for saphenous veins and every 5-10 cm for others) into the varicose veins. When the contrast medium in the target vessels was replaced by the hypointense foam sclerosant or on signs of foam entry into the perforator veins under fluoroscopy, the injection was stopped and the site was manually pressed. All patients received postprocedure compression with elastic bandages until ulcer healing and compression stockings (30-40 mm Hg) thereafter. A total of 35 patients (42 limbs) were included. The maximal ulcer diameter was 3.6 ± 1.4 cm (range, 1.1-5.8 cm). The number of injection sites ranged from 3 to 10; total foam amount ranged from 4.5 to 35 mL. All 35 patients completed 12-month follow-up. Ulcer healing rate was 100%, and 1-year recurrence rate was 2.9%. The Venous Clinical Severity Score was 12.98 ± 3.91 before treatment, decreasing to 3.02 ± 2.39 at 12 months (P < .01). Superficial thrombophlebitis developed in 21 (50%) limbs. No deep venous thrombosis or pulmonary embolism was observed during follow-up. Among the 33 limbs (27 patients) with ultrasound examination at 12 months, 28 (84.8%) limbs had complete occlusion and the remaining 5 (15.2%) had recanalization. Ultrasound- and fluoroscopy-guided foam sclerotherapy is safe and effective for the treatment of venous ulcers of the lower extremities. Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.