Purpose To evaluate the efficacy and safety of ultrasound-guided femoral nerve block (FNB) in treating great saphenous vein (GSV) insufficiency by endovenous radiofrequency ablation (EVRA) combined with punctate stripping (PS). Methods This was a single-center, retrospective cohort study. A total of 135 patients were divided into Group A (59 patients) and Group B (76 patients). All patients received tumescent anesthesia during the operation, and group A received an additional ultrasound-guided FNB before the procedure. Intraoperative and postoperative pain score, the volume of tumescent anesthesia solution (TAS), and other indicators were compared in two groups. Results Group A had a significantly lower intraoperative pain visual analog scale than group B (2.7 ± 1.2 vs 5.2 ± 1.5, P < 0.001). The volume of TAS in group A was significantly lower than that in group B (198 ± 26.6 ml vs 338 ± 34.7 ml, P < 0.001). Postoperative muscle strength of group A was significantly decreased compared with group B (54.2% vs 3.90%, P < 0.001); no patient had severe limitation of active movements in both groups, and all motor blocks recovered within 24 h. The incidence of skin ecchymosis in group A was lower than that in group B (18.6% vs 46.1%, P = 0.001). The operation duration of the two groups had no statistically significant difference. Conclusions Ultrasound-guided FNB in treating GSV insufficiency by EVRA combined with PS significantly relieved intraoperative pain and reduced the dosage of TAS and the incidence of skin ecchymosis without increasing the complications of anesthesia or any other surgical complications.