Percutaneous vertebroplasty is an efficient procedure to treat pain due to osteoporotic vertebral compression fractures. However, refracture of cemented vertebrae occurs occasionally after vertebroplasty. It is unclear whether such fractures are procedure-related or part of the natural course of osteoporosis. The effect of potentially important covariates on refracture risk in cemented vertebrae has not been evaluated previously. We retrospectively analyzed the incidence and possible causative mechanism of refracture in patients who had received only one vertebroplasty for a single level of vertebral compression fracture. We assessed the following covariates: age, sex, body weight, height, lumbar spine bone mineral density, treated vertebral level, pre-existing untreated vertebral compression fracture, and gas-containing vertebrae before treatment. Surgical variables, including surgical approach, cement injected, and anterior vertebral height restoration, were also analyzed. Anti-osteoporotic treatment after surgery was recorded. Multiple logistic regression analysis was used to determine the relative risk of refractures of cemented vertebrae. Over all, 98 patients were evaluated with a mean follow-up of 26.9 +/- 12.4 months (range, 7-55 months). We identified 62 refractures and the mean loss of anterior vertebral height was 13.3% (range 3.2-40.3%). The greater the anterior vertebral height obtained from vertebroplasty, the greater the risk of refracture occurring (P < 0.01). Gas-containing vertebrae were also prone to refracture after the procedure (P = 0.01). Anti-osteoporotic treatment was of borderline significance between refractured and non-refractured vertebrae (P = 0.07). Only restoration of anterior vertebral height was positively associated with refracture during the follow-ups (P < 0.01). In conclusion, refractures of cemented vertebrae after vertebroplasty occurred in 63% of osteoporotic patients. Significant anterior vertebral height restoration increases the risk of subsequent fracture in cemented vertebrae.