BACKGROUND: The cortical bone trajectory (CBT) has attracted attention as a new minimally invasive technique for lumbar instrumentation by minimizing soft-tissue dissection. Biomechanical studies have demonstrated the superior fixation capacity of CBT; however, there is little consensus on the selection of screw size, and no biomechanical study has elucidated the most suitable screw size for CBT. The purpose of the present study was to evaluate the effect of screw size on fixation strength and to clarify the ideal size for optimal fixation using CBT. METHOD: A total of 720 analyses on CBT screws with various diameters (4.5-6.5 mm) and lengths (25-40 mm) in simulations of 20 different lumbar vertebrae (mean age: 62.1 ± 20.0 years, 8 males and 12 females) were performed using a finite element method. First, the fixation strength of a single screw was evaluated by measuring the axial pullout strength. Next, the vertebral fixation strength of a paired-screw construct was examined by applying forces simulating flexion, extension, lateral bending, and axial rotation to the vertebra. Lastly, the equivalent stress value of the bone-screw interface was calculated. RESULTS: Larger-diameter screws increased the pullout strength and vertebral fixation strength and decreased the equivalent stress around the screws; however, there were no statistically significant differences between 5.5-mm and 6.5-mm screws. The screw diameter was a factor more strongly affecting the fixation strength of CBT than the screw fit within the pedicle (%fill). Longer screws significantly increased the pullout strength and vertebral fixation strength in axial rotation. The amount of screw length within the vertebral body (%length) was more important than the actual screw length, contributing to the vertebral fixation strength and distribution of stress loaded to the vertebra. CONCLUSIONS: The fixation strength of CBT screws varied depending on screw size. The ideal screw size for CBT is a diameter larger than 5.5 mm and length longer than 35 mm, and the screw should be placed sufficiently deep into the vertebral body.