Objective To compare the effect of high ligation and spot stripping (HLSS) and high ligation and foam sclerotherapy (HLFS) in the treatment of great saphenous varicose veins (GSVV). Methods A retrospective analysis was conducted on the clinical data of 385 patients with GSVV who received HLFS or HLSS treatment at Guizhou Provincial People’s Hospital from January 2018 to June 2022. The differences in surgical time, intraoperative bleeding, complications, and postoperative hospital stay between the two groups were compared. Results The surgical time, intraoperative bleeding, postoperative hospital stay, visual analog scale for pain, incidence of postoperative hematoma, skin sensory disorders, and infection in the HLFS group were less or lower than those in the HLSS group (P<0.05), but there was no statistically significant difference in recurrence rate between the two groups (P>0.05). Compared with preoperative indicators at the same group, the modified venous clinical severity score (VCSS) decreased and the chronic lower limb venous insufficiency questionnaire (CIVIQ) score increased (P<0.05). However, there was no statistically significant difference in the degree of improvement in VCSS and CIVIQ between the two groups at three months after surgery and before surgery (P>0.05). Conclusions HLFS has a definite therapeutic effect on GSVV, with smaller trauma, faster recovery after surgery, and lower incidence of postoperative complication compared to HLSS. It can be used as a surgical option for GSVV patients in clinical practice.