The assessment of a human vertebra’s stability after a screws fixation procedure and its fracture risk is still an open clinical problem. The accurate evaluation of fracture risk requires that all fracture mechanical determinants such as geometry, constitutive behavior, loading modes, and screws angulation are accounted for, which requires biomechanics-based analyses. As such, in the present work we investigate the effect of pedicle screws angulation on a patient-specific model of non osteoporotic lumbar vertebra, derived from clinical CT images. We propose a novel computational approach of fracture analysis and compare the effects of fixation stability in the lumbar spine. We considered a CT-based three-dimensional FE model of bilaterally instrumented L4 vertebra virtually implanting pedicle screws according to clinical guidelines. Nine screws trajectories were selected combining three craniocaudal and mediolateral angles, thus investigated through a parametric computational analysis. Bone was modeled as an elastic material with element-wise inhomogeneous properties fine-tuned on CT data. We implemented a custom algorithm to identify the thin cortical layer correctly from CT images ensuring reliable material properties in the computational model. Physiological motion (i.e., flexion, extension, axial rotation, lateral bending) was further accomplished by simultaneously loading the vertebra and the implant. We simulated local progressive damage of the bone by using a quasi-static force-driven incremental approach and considering a stress-based fracture criterion. Ductile-like and brittle-like fractures were found. Statistical analyses show significant differences comparing screws trajectories and averaging the results among six loading modes. In particular, we identified the caudomedial trajectory as the least critical case, thus safer from a clinical perspective. Instead, medial and craniolaterally oriented screws entailed higher peak and average stresses, though no statistical evidence classified such loads as the most critical scenarios. A quantitative validation procedure will be required in the future to translate our findings into clinical practice. Besides, to apply the results to the target osteoporotic population, new studies will be needed, including a specimen from an osteoporotic patient and the effect of osteoporosis on the constitutive model of bone.