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Objective To develop a novel screw positioning method to improve the treatment of unstable thoracolumbar fractures. Methods A total of 72 patients with unstable thoracolumbar fractures who were treated with anterior screw–rod interfixation from January 2011 to October 2015 were included in this clinical study. Those patients included 48 male and 24 female patients with an average age of 45.10 years (range, 26–63 years). Patients were randomly divided into two groups: an observation group (n = 36) and a control group (n = 36). The quadrant positioning method was used for screw insertion in the observation group during the operation, while the traditional screw positioning method was used in the control group. The quadrant positioning method targeted four quadrants, including the superior anterior (SA), superior posterior (SP), inferior anterior (IA) and inferior posterior (IP) quadrants, while for the traditional screw positioning, four screws were inserted into the vertebral bodies above and below the excision. Patients were followed up for approximately 40 months to record recovery. Clinical and radiological records, local angle and fractured vertebra body height, clinical outcomes, complications, neurological improvement, and fusion rate were recorded and compared between the two groups. Results The quadrant positioning method was successfully used for anterior screw insertion. The quadrant center in the lateral view of the vertebral body was well marked, and screws were easily located on the scheduled quadrant. Blood loss (BL), hospital stay (HS), and operation time (OP) in the observation group were 749.40 ± 379.90 mL, 17.10 ± 4.10 days, and 167.40 ± 44.70 min, respectively. While those parameters in the control group were 1198.40 ± 339.27 mL, 23.22 ± 3.77 days, and 221.47 ± 32.15 min, respectively. The average operation time and hospital stay time were significantly shorter, and blood loss was significantly less in the observation group than in the control group (P