Objective: To compare the functional and radiological outcome of different approaches of percutaneous vertebroplasty (PVP) in the treatment of osteoporotic vertebral compression fractures (OVCF), and to analyze the factors affecting postoperative re-fracture in patients with OVCF. Methods: Medical data of 76 patients with OVCF who underwent PVP in our hospital from January 2021 to December 2021 were analyzed retrospectively. Based on the different intraoperative approaches, patients were divided into Unilateral-group (n=36) and Bilateral-group (n=40). The perioperative indexes, clinical efficacy, and spinal nerve function of the two groups were compared. Logistic regression analysis was used to determine the risk factors of postoperative re-fracture in patients with OVCF. The functional outcome was assessed with Oswestry disability index (ODI), American Spinal Injury Association (ASIA) nerve function classification and pain with Visual analogue scale (VAS). The radiological outcome was assessed by noting change of anterior vertebral height and change of kyphosis Cobb angle. Results: The amount of intraoperative bleeding, the number of X-ray irradiation and the volume of injected bone cement in the Unilateral-group were lower, and the operation time was shorter than Bilateral-group (all P<0.05). One week after the operation, the anterior height of the vertebral body was higher, the Cobb angle of kyphosis was lower, the VAS score was higher, and the ASIA grade was lower in the Unilateral-group compared to the Bilateral-group (P<0.05). Logistic regression analysis showed that the age, bone mineral density, volume of bone cement injection and PD were risk factors of postoperative re-fracture in patients with OVCF. Conclusion: Unilateral PVP treatment of OVCF has the advantages of less intraoperative bleeding, less X-ray irradiation and shorter operation time. At the same time, bilateral PVP is associated with improved bone cement dispersion, and the effect of improving patients’ pain is better than that in the Unilateral PVP. Postoperative risk of re-fracture in OVCF patients correlated with age, bone mineral density, amount of bone cement injection and pedicle diameter. doi: https://doi.org/10.12669/pjms.39.1.7069 How to cite this: Bu D, He X. Comparison of different approaches of percutaneous vertebroplasty in the treatment of osteoporotic spinal compression fractures and analysis of influencing factors of re-fracture. Pak J Med Sci. 2023;39(1):---------. doi: https://doi.org/10.12669/pjms.39.1.7069 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.