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Bing Tan, Qi-Yuan Yang, Bin Fan, Qin Li, Xiao-Yan Zhang Department of Spine Surgery, The Third Hospital of MianYang, Sichuan Mental Health Center, Mianyang, Sichuan Province, 621000, People’s Republic of ChinaCorrespondence: Qi-Yuan Yang, Department of Spine Surgery, The Third Hospital of MianYang, Sichuan Mental Health Center, Mianyang, Sichuan Province, 621000, People’s Republic of China, Tel +8615882889797, Email qiyuan5988@163.comPurpose: This study aimed to explore the effectiveness and safety of digital subtractionangiography (DSA)-guided percutaneous kyphoplasty (PKP) in treating multi-segmental osteoporotic vertebral compression fracture (OVCF).Methods: We retrospectively reviewed 68 patients with multi-segmental OVCF who had unilateral PKP surgeries using DSA and C arm guiding at our hospital between October 2016 and June 2020 and were followed for at least two years. All patients were divided into two groups: DSA guidance (n = 31) and C‐arm guidance (n=37). In addition, we collected the clinical and radiological evaluation results during postoperative and last follow-up periods.Results: Our findings revealed that the DSA guidance group required lesser time for channel establishment and surgery than the C-arm guidance group at P < 0.05. The incidences of bone cement leakage, fluoroscopy times, and radiation dose of the DSA guidance group were significantly lesser than the C‐arm guidance group (P < 0.05). Compared to the C-arm guidance group, the deviation of puncture in the DSA guidance group was significantly lower, the puncture angle in the DSA guidance group was significantly larger, and better bone cement distribution was obtained (P < 0.05). Compared to preoperative data, the VAS score, median vertebral height, and Cobb angle were significantly improved one day after surgery and the final follow-up in both groups (P < 0.05). However, the VAS score, the median vertebral height, average length of stay, and Cobb angle were not significantly different between the two groups (P > 0.05).Conclusion: DSA-guided PKP in treating multi-segmental OVCF can shorten the operation time, improve puncture accuracy, reduce the times and dose of fluoroscopy, reduce the leakage of bone cement, and achieve better cement distribution.Keywords: digital subtraction angiography, percutaneous kyphoplasty, multi-segmental osteoporotic vertebral compression fracture