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This study aimed to assess the accuracy of cortical bone trajectory (CBT) screws placement guided by a spinous process clamp (SPC) guide. A total of 32 patients who received single-level midline lumbar fusion (MIDLF) surgery between June 2019 and January 2020 were retrospectively analyzed and divided into free-hand (FH) and SPC-guided groups according to the surgical approach. In the FH group, CBT screws was implanted with the assistance of fluoroscopy, while in the SPC group, CBT screws was implanted using the SPC navigator hardwire. A total of 128 screws were assessed in this study, with higher rates of clinically acceptable screw placement (grades A and B) and grade A screws in the SPC group than in the FH guide group (92.2% vs. 79.7%, P = 0.042 and 54.7% vs. 35.9%, P = 0.033, respectively). Misplacement screws (grades C, D, and E) occurred more often in the FH group than in the SPC guide group (20.3% vs. 7.8%, P = 0.042). The incidence of proximal facet joint violation (FJV) was higher in the FH group than in the SPC group (15.6% vs. 3.1%, P = 0.030). The radiation dose and time in the SPC guide group were comparable to those in the FH group (P = 0.063 and P = 0.078). The average operative time was significantly longer in the SPC guide group than in the FH group (267.8 ± 45.5 min vs. 210.9 ± 44.5 min, P = 0.001). Other clinical parameters, such as the average bone mineral density (BMD), intraoperative blood loss, and postoperative hospital stay, were not significantly different. Oswestry disability index (ODI) and back pain visual analogue scale (VAS) scores were significantly improved in both groups compared with preoperatively. SPC guided screw placement was more accurate than the fluoroscopy-assisted FH technique for single-level MIDLF at L4/5. Patients undergoing SPC-guided screw placement can achieve similar clinical outcomes as the fluoroscopy-assisted FH technique. [ABSTRACT FROM AUTHOR]