Objective Endoscopic surgeries have been attempted in the field of lumbar decompression and fusion surgery in the past decade. Percutaneous endoscopic lumbar interbody fusion (PELIF) is a new-emerging technique taking advantages of an anatomical (Kambin's triangle) to achieve simultaneous decompression and fusion under endoscopic visualization. The purpose of this study is to evaluate the feasibility and safety of PELIF technique with general anesthesia and neuromonitoring. Methods The authors present the details of PELIF technique with general anesthesia and neuromonitoring. The first 7 consecutive patients treated with minimum of 2 year's follow-up were included. Clinical outcomes were assessed by visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) in the immediate preoperative period and during the follow-up period. Results All patients underwent single-level PELIF surgery successfully and without conversion to open surgery. The average age was 56.0±13.0 years. All patients had Grade I degenerative/isthmic spondylolisthesis and 4 patients coexisted with disc herniation. The mean operative time was 167.5±30.9 minutes, and intraoperative blood loss was 70.0±24.5 ml. Postoperative drainage volume was 24.5±18.3 ml. The differences in the VAS scores for low back pain and leg pain between preoperative and follow-up were significant (P<0.05). The SF-36 Physical Component Summary (PCS) improved from 38.83±4.17 to 55.67±2.58 (P<0.001). The SF-36 Mental Component Summary (MCS) improved from 43.83±3.13 to 57.50±5.36 (P=0.001). The ODI score improvement rate was 33.7±3.7 %. All cases demonstrated radiopaque graft in the intervertebral disc space consistent with solid arthrodesis. Conclusions PELIF technique seems to be a promising surgical technique for selected appropriate patients, with the minimal invasive advantages in decreased blood, shortage of ambulation time, and hospital stay, compared with MIS-TLIF. Because of limited Kambin's triangle space and the exiting nerve root nearby, PELIF is still a challenging technique. Future advancement and development in instrument and cage design are vital for application and popularization of this technique. Prospective, randomized, controlled studies with large sample size on PELIF technique are still needed to prove its safety, efficacy, and minimal invasive advantages.