OBJECTIVE: To evaluate the safety and efficacy of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) with an expandable cage for the treatment of single-level degenerative lumbar spinal stenosis (LSS) with instability. METHODS: The clinical data of 42 patients (14 males and 28 females) with single-level LSS with instability who underwent PE-TLIF from September 2019 to April 2023 were retrospectively reviewed. All the patients underwent a minimum follow-up of 12 months. The demographics and perioperative and clinical outcomes were reviewed on the basis of the visual analog scale score, Oswestry Disability Index, and modified MacNab criteria. The Brantigan criteria were used to assess interbody fusion at the final follow-up. RESULTS: The mean age was 69.57 ± 6.06 (61-81) years. The average surgical time was 157.02 ± 13.80 minutes (range, 140-220 minutes). The mean estimated blood loss was 48.09 ± 15.22 mL (range, 20-80 mL). The preoperative visual analog scale scores for back pain and leg pain were 6.76 ± 0.88 and 6.90 ± 0.91, respectively, and the preoperative Oswestry Disability Index score was 66.47 ± 7.57. The respective values were 1.83 ± 0.44, 1.79 ± 0.52, and 19.76 ± 6.08 at 12 months postoperatively. According to the modified MacNab criteria, 85.71% (36/42) of patients exhibited good-to-excellent outcomes. The interbody fusion rate was 100% at the final follow-up. Two patients had postoperative intraspinal hematomas, one of whom had cauda equina syndrome and underwent reoperation. Two patients with osteoporosis experienced mild cage subsidence. However, their low back pain was significantly relieved, and interbody fusion was detected at the final follow-up. CONCLUSIONS: For patients with single-level LSS with instability, PE-TLIF with an expandable cage under conscious sedation and local anesthesia potentially represents an effective method for treating degenerative LSS with instability.