The aim of this study is to compare the surgical outcomes of two different surgical approaches, open transforaminal lumbar interbody fusion (TLIF) and Wiltse TLIF, in the treatment of single-level lumbar spondylolisthesis and also to provide the advantages and disadvantages of each approach. This retrospective study included 600 patients with single-level lumbar spondylolisthesis who underwent fusion surgery at a single academic institution between January 2018 and December 2022. Patients were divided into two groups: traditional open TLIF (group A; 300 patients) and the Wiltse TLIF approach (group B; 300 patients). Preoperative diagnostic tests were performed on all patients. The fluoroscopy time for the Wiltse TLIF group was longer, whereas the mean blood loss for the Wiltse TLIF approach was less. Both techniques resulted in significant improvements in pain relief and functional disability, with no significant difference between the two groups in terms of their pre- or post-operative (Oswestry Disability Index) ODI scores. The Wiltse TLIF technique resulted in significantly shorter hospital stays and had a lower rate of complications compared with the open TLIF technique. The Wiltse TLIF approach showed advantages in shorter surgical times, reduced blood loss, and shorter hospital stays, whereas the traditional open TLIF approach exhibited shorter fluoroscopy times.