Objective: The purpose of this study was to compare the safety and efficacy of ultrasound and fluoroscopy-guided for determining the puncture entry point of percutaneous vertebroplasty (PVP). Methods: From November 2018 to December 2019, a total of 50 eligible patients with thoracolumbar osteoporotic vertebral compression fractures (OVCFs) treated by PVP were retrospectively collected, of which 25 cases were in ultrasound-guided group and the other 25 cases were in fluoroscopy-guided group. Radiation doses, one-time localization success rate, operation time, clinical efficacy and complications incidence were compared between the two groups.Results: Ultimately, 46 patients completed followed-up, whose average follow-up time was 9 months, the dose and times of fluoroscopy and operation time in ultrasound-guided group statically significantly decreased compared to fluoroscopy-guided group (P<0.01). The one-time localization success rate in ultrasound-guided group and fluoroscopy-guided group were 68.2% and 37.5% respectively (x2= 4.33, P=0.037), whose difference was statistically significant (P<0.01). However, there was no significant difference in the visual analog scale (VAS) scores of back pain relief between the two groups (P>0.05). There were no postoperative complications such as infection, hematoma formation and fracture nonunion obsereved between the two groups.Conclusion: Ultrasound-guided entry point determination for PVP puncture is safe, which can significantly improve the success rate of one-time localization and decrease radiation exposure and operation time.