BACKGROUND To compare efficacy and safety of percutaneous transforaminal endoscopic spine system (TESSYS) and traditional fenestration discectomy (FD) in treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS A total of 106 LDH patients were divided into TESSYS group (n=48) and FD group (n=58). Visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association (JOA), and modified MacNab criteria were used for efficacy evaluation. Post-operative responses were compared by enzyme-linked immunosorbent assay (ELISA) based on detection of serum IL-6, CRP, and CPK levels. RESULTS In the TESSYS group, compared with the FD group, we observed, shorter incision length, less blood loss, shorter hospital stay, lower hospitalization cost, shorter recovery time, lower complication rate (all P<0.001), and lower VAS scores of lumbago and skelalgia at 3 days and 1, 3, and 6 months postoperatively (all P<0.05). At 24 and 48 h postoperatively, CRP level was remarkably higher in the FD group compared to the TESSYS group (P<0.001). Further, comparison of IL-6 levels at 6, 12, 24, and 48 h postoperatively revealed significantly higher levels in the FD group than in the FESSYS group (all P<0.001). CONCLUSIONS TESSYS had clinical advantages over FD and entails less trauma and quicker postoperative recovery, suggesting that TESSYS is well tolerated by patients and is a better approach than FD in surgical treatment of LDH.