This study evaluated the risk factors of new vertebral compression fractures (VCFs) following percutaneous vertebroplasty (PVP). From June 2005 to January 2011, patients with osteoporotic VCFs (OVCFs) who were treated with PVP and met this study's inclusion criteria were retrospectively reviewed. Observed parameters were age, sex, bone mineral density, body mass index, amount of bone cement, cement leakage into the disk, preoperative kyphosis, preoperative degree of anterior vertebral compression, preoperative degree of middle vertebral compression, kyphosis correction, anterior vertebral height restoration, middle vertebral height restoration, and number of initial symptomatic fractures (levels treated). The data were analyzed by univariate and multivariate analysis for the emergence of new fractures after PVP to determine related risk factors. A total of 182 patients met the inclusion criteria. There were 155 female and 27 male patients with a mean age of 69.7 years (range 49-91 years). The follow-up period was 24-50 months (average 26.4 months). A total of 294 VCFs among 182 patients were observed, 28 new VCFs occurred in 21 patients (21/182, 11.5 %) during the follow-up period. Statistical analysis indicated that higher BMI (P = 0.004) and a greater number of initial symptomatic fractures (P = 0.017) were significantly associated with new VCFs after PVP. It is the most obvious that the risk of new fractures increased 2.518-fold (95 % CI 1.176-5.395), when the number of initial VCFs increased by one level. The incidence of new symptomatic VCFs after PVP was higher in osteoporotic patients with initial multiple-level fractures.