To better understand the risk of secondary vertebral compression fracture (VCF) following a vertebroplasty or kyphoplasty, we compared patients treated with those procedures to patients with a previous VCF. The risk of subsequent fracture was significantly greater among treatment patients, especially within 90 days of the procedure. Introduction: Predominantly uncontrolled studies suggest a greater risk of subsequent vertebral compression fractures (VCFs) associated with vertebroplasty/kyphoplasty. To further understand this risk, we conducted a population-based retrospective cohort study using data from a large regional health insurer. Methods: Administrative claims procedure codes were used to identify patients receiving either a vertebroplasty or kyphoplasty (treatment group) and a comparison group of patients with a primary diagnosis of VCF who did not receive treatment during the same time period. The main outcomes of interest, validated by two independent medical record reviewers, were any new VCFs within (1) 90 days, (2) 360 days, and (3) at adjacent vertebral levels. Multivariable logistic regression examined the association of vertebroplasty/kyphoplasty with new VCFs. Results: Among 48 treatment (51% vertebroplasty, 49% kyphoplasty) and 164 comparison patients, treated patients had a significantly greater risk of secondary VCFs than comparison patients for fractures within 90 days of the procedure or comparison group time point [adjusted odds ratio (OR)∈=∈6.8; 95% confidence interval (CI) 1.7-26.9] and within 360 days (adjusted OR∈=∈2.9; 95% CI 1.1-7.9). Conclusions: Patients who had undergone vertebroplasty/kyphoplasty had a greater risk of new VCFs compared to patients with prior VCFs who did not undergo either procedure. © 2008 International Osteoporosis Foundation and National Osteoporosis Foundation.