Objective To study efficacy of ligation and stripping of great saphenous vein in combination with foam sclerotherapy and foam sclerotherapy alone in treatment of venous leg ulcer. Method Fifty-seven patients with venous leg ulcers from January 2015 to December 2016 in the West China Hospital of Sichuan University were collected, then were designed to ligation and stripping of great saphenous vein in combination with foam sclerotherapy group (abbreviated as combination therapy group, n=33) and foam sclerotherapy alone group (n=24). Results The baseline data such as the age, gender, disease duration, and ulcer size had no significant differences in these two groups (P>0.05). All the patients received operation successfully. The median operative time was shorter, the average intraoperative blood loss was less, and the time of ulcer healing after surgery was longer in the foam sclerotherapy alone group as compared with the combination therapy group [14 minversus 40 min, P<0.001; (12.3±3.2) mLversus (35.5±10.0) mL, P<0.001; (22.0±4.5) dversus (13.7±4.0) d, P<0.001]. The rates of the wound infection, local pigmentation, and ulcer recurrence had no significant differences between the foam sclerotherapy alone group and the combination therapy group (4.2%versus 9.1%, P=0.472; 25.0% versus 15.2%, P=0.352; 20.8% versus 9.1%, P=0.208). The foam sclerotherapy alone group was obviously superior to the combination therapy group in the time and cost of hospitalization (4 d versus 13 d, P<0.001; 3 000 yuanversus 8 590 yuan, P<0.001). There was no large area of tissue necrosis, the deep vein thrombosis, or the other serious complications in these two groups. Conclusion Ligation and stripping of great saphenous vein in combination with foam sclerotherapy in treatment of venous leg ulcer can accelerate ulcer healing than foam sclerotherapy alone, but there is no significant difference between these two groups in complications and recurrence rate, the foam sclerotherapy alone group is superior in time and cost of hospitalization, appropriate treatment plan should be formulated according to specific situation of patient.