STUDY DESIGN: A prospective, randomized controlled study of patients with L5-S1 lumbar disc herniations, operated with endoscopic discectomy through an interlaminar or transforaminal approach. OBJECTIVE: To compare the results of percutaneous endoscopic lumbar discectomy in L5-S1 disc herniation through an interlaminar or transforaminal approach. SUMMARY OF BACKGROUND DATA: The transforaminal and interlaminar techniques are both acceptable approaches for L5-S1 disc herniation. This is the first study to compare these two approaches in terms of their surgical effects and advantages. METHODS: From January 2010 to June 2010, 60 patients with L5-S1 disc herniation were randomly recruited into two groups; one group underwent percutaneous endoscopic interlaminar discectomy (PEID) and the other group underwent percutaneous endoscopic transforaminal discectomy (PETD). There were 30 patients in each group. The operation time, intraoperative radiation time, postoperative bed rest time, hospitalization time, and complications were compared between the groups. The surgical effectiveness was assessed according to the Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and modified MacNab criteria. RESULTS: All the patients completed follow up with a mean of 27.6 months (range, 24-37 months). In the PEID group, the mean operation time was 65.0 ± 14.9 minutes, and the intraoperative radiation time was 0.60 ± 0.24 seconds. For the PETD group, the mean operation time was 86.0 ± 15.4 minutes, and the intraoperative radiation time was 6.50 ± 1.52 seconds. There were significant differences in operation time and radiation time between the two groups (P < 0.01) but not in the postoperative bed rest time, hospitalization time, or complication rate (P > 0.05). The postoperative ODI and VAS were obviously improved in both groups when compared with preoperation (P < 0.01). According to the MacNab criteria, the satisfactory rates were 93.3% and 90.0% in the two groups, without a significant difference (P > 0.05). CONCLUSION: PEID can escape the blockade of crista iliaca, and advantages include a faster puncture orientation, a shorter operation time, and less intraoperative radiation exposure. PETD requires higher punctuation skill and more intraoperative radiation exposure. LEVEL OF EVIDENCE: 4.