OBJECTIVE: Both the paraspinal muscle sparing approach and percutaneous screw fixation are less traumatic procedures in comparison with the conventional midline approach. These techniques have been used with the goal of reducing muscle injury. The purpose of this study was to evaluate and to compare the safety and efficacy of the paraspinal muscle sparing technique and percutaneous screw fixation for the treatment of L5-S1 spondylolisthesis. METHODS: Twenty patients who had undergone posterior lumbar interbody fusion (PLIF) at the L5-S1 segment for spondylolisthesis were prospectively studied. They were divided into two groups by screw fixation technique (Group I : paraspinal muscle sparing approach and Group II: percutaneous screw fixation). Clinical outcomes were assessed by Low Back Outcome Score (LBOS) and Visual Analogue Scale (VAS) for back and leg pain at different times after surgery. In addition, modified MacNab's grading criteria were used to assess subjective patients' outcomes 6 months after surgery. Postoperative midline surgical scarring, intraoperative blood loss, mean operation time, and procedure-related complications were analyzed. RESULTS: Excellent or good results were observed in all patients in both groups 6 months after surgery. Patients in both groups showed marked improvement in terms of LBOSs all over time intervals. Postoperative midline surgical scarring and intraoperative blood loss were lower in Group II compared to Group I although these differences were not statistically significant. Low back pain (LBP) and leg pain in both groups also showed significant improvement when compared to preoperative scores. However, at 7 days and 1 month after surgery, patients in Group II had significantly better LBP scores compared to Group I. CONCLUSION: In terms of LBP during the early postoperative period, patients who underwent percutaneous screw fixation showed better results compared to ones who underwent screw fixation via the paraspinal muscle sparing approach. Our results indicate that the percutaneous screw fixation procedure is the preferable minimally invasive technique for reducing LBP associated with L5-S1 spondylolisthesis.