Objective: To investigate the clinical efficacy of subfascial endoscopic perforator vein surgery (SEPS) in treatment of lower extremity venous ulcers (venous leg ulcers, VLU). Methods: The clinical data of 70 patients (76 affected legs) with chronic venous insufficiency (CVI) of lower limb admitted within three and a half years were retrospectively analyzed. According to CEAP clinical classification, 38 cases (41 affected legs) were classified as stage C4, 18 cases (18 affected legs) as C5 and 14 cases as C6, respectively. Of the patients, 18 C4 cases (18 affected legs) underwent high ligation and short segment stripping of the greater saphenous vein (traditional group), and all of the other cases underwent SEPS procedure combined with high ligation and short segment stripping of the greater saphenous vein (SEPS group). The CEAP clinical scores of the affected legs before and after operation, and ulcer healing time and recurrence of the affected legs were analyzed. Results: In the patients of SEPS group, the varicosities disappeared after surgery, dull ache and heavy sensation of the affected leg were gradually alleviated, and local itching and ulcer wound surface pain were relieved; the pigmentation and induration in the area of healed ulcerations were obviously improved, and dermatitis disappeared in C5 patients; the active ulcers in the gaiter area in C6 patients healed within 10–60 d (average of 47.3 d) after surgery; the postoperative CEAP clinical scores of the affected legs were all lower than those before surgery (all P<0.05), and no recurrence was seen during the follow-up period (average of 15 months). No significant differences were noted in the clinical scores between the C4 patients who underwent SEPS and no SEPS (all P>0.05). Conclusion: SEPS is an effective treatment method for severe low limb CVI with VLU.