Objective To compare the effectiveness of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) and Wiltse-approach transforaminal lumbar interbody fusion (W-TLIF) in the treatment of lumbar spondylolisthesis. Methods The clinical data of 47 patients with lumbar spondylolisthesis who underwent surgery and met the selection criteria between July 2018 and June 2019 were retrospectively analyzed, in which 21 patients were treated with PE-TLIF (PE-TLIF group) and 26 patients were treated with W-TLIF (W-TLIF group). There was no significant difference between the two groups in age, gender, disease duration, spondylolisthesis vertebra, spondylolisthesis degree, spondylolisthesis type, and preoperative low back pain and leg pain visual analogue scale (VAS) score, lumbar Japanese Orthopaedic Association (JOA) score, and the disc height (DH), segmental lordosis (SL), and Taillard index (TI) of the operated level (P>0.05). The operation time, intraoperative blood loss, postoperative drainage, postoperative bedridden time, and complications were compared between the two groups. The VAS score and JOA score were used to evaluate the improvement of pain and function. At last follow-up, DH, SL, and TI were measured by X-ray films, and lumbar CT was performed to evaluate the interbody fusion. Results Compared with W-TLIF group, the operation time in PE-TLIF group was significantly longer, but the intraoperative blood loss and postoperative drainage were less, and the postoperative bedridden time was shorter (P<0.05). There were 2 cases of transient lower limb radiating pain in PE-TLIF group and 1 case of superficial incision infection in W-TLIF group. There was no significant difference in the incidence of complications (9.5% vs. 3.8%) between the two groups (χ2=0.037, P=0.848). The patients in both groups were followed up 12-24 months, with an average of 17.3 months in PE-TLIF group and 17.7 months in W-TLIF group. The VAS scores of low back pain and leg pain, and the JOA scores of the two groups were significantly improved at each time point after operation when compared with those before operation (P<0.05). Compared with W-TLIF group, the VAS scores of low back pain in PE-TLIF group were significantly lower at 3 days and 3 months after operation (P<0.05), and the JOA score of PE-TLIF group was significantly higher at 3 months after operation (P<0.05), and there was no significant difference in each score at any other time point between the two groups (P>0.05). At last follow-up, the DH, SL, and TI of the two groups were significantly improved when compared with those before operation (P<0.05), and there was no significant difference in the differences of each parameter between the two groups (P>0.05). According to Suk’s standard, the fusion rates of PE-TLIF group and W-TLIF group were 90.5% (19/21) and 92.3% (24/26), respectively, with no significant difference (χ2=0.000, P=1.000). At last follow-up, there was no case of Cage sunk into the adjacent vertebral body, or dislodgement of Cage anteriorly or posteriorly in both groups. Conclusion PE-TLIF and W-TLIF are both effective in the treatment of grade Ⅰ and Ⅱ lumbar spondylolisthesis. Although the operation time is prolonged, PE-TLIF has less intraoperative blood loss and postoperative drainage, shorter postoperative bedridden time, and can get more obvious short-term improvement of low back pain and function.