The purpose of this retrospective study was to assess the clinical outcomes of discectomy by using full-endoscopic visualization technique via the interlaminar approach versus the transforaminal approach under general anesthesia in the treatment of L5-S1 disc herniation.Sixty patients with L5-S1 disc herniation were non-randomly recruited and assigned into two groups. One group (thirty patients) underwent discectomy by using full-endoscopic visualization technique via the interlaminar approach under general anesthesia, while the other group (thirty patients) underwent discectomy by using full-endoscopic visualization technique via the transforaminal approach under general anesthesia. The operative time, fluoroscopy time, and perioperative complications were recorded. The visual analog scale (VAS) score for leg and back pain and Oswestry disability index (ODI) score were evaluated preoperatively and at 3, 6, and 18 months postoperatively.The mean operative time and fluoroscopy time in the interlaminar group were significantly shorter compared with those in the transforaminal group. The mean VAS and ODI postoperative scores were significantly improved over the preoperative scores in both groups. According to the MacNab classification system, more than 90.0% of the patients achieved an excellence/good rating in both groups. An intraoperative epineurium injury occurred in both groups. The total recurrence rate during 18 months follow-up was 3.3% in the interlaminar group and 0% in the transforaminal group.It is efficient and safe to perform discectomy by using full-endoscopic visualization technique via both interlaminar and transforaminal approaches under general anesthesia in patients with L5-S1 disc herniation. Discectomy performed by using full-endoscopic visualization technique via the interlaminar approach requires a shorter operative time and suffers less radiation exposure than the transforaminal approach.