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Background: Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5-S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5-S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5-S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively)., Methods: One hundred twenty-three patients with L5-S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA., Results: VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group., Conclusion: Disc herniation at the L5-S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.