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Background: We performed a meta-analysis to evaluate the efficacy and safety of zoledronic acid combined with percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fractures (OVCFs).Methods: Eligible scientific articles published prior to July 2020 were retrieved from the PubMed, Springer, ScienceDirect, and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1.Results: Three randomized controlled trials (RCTs) and 2 non-RCTs met the inclusion criteria. The present meta-analysis revealed that zoledronic acid combined with PKP is associated with a higher BMD, a better quality of life, less severe low back pain, and fewer additional vertebral body fractures than is percutaneous vertebral augmentation alone.Conclusions: Compared with PKP only, zoledronic acid combined with percutaneous vertebral augmentation is beneficial for OVCFs.