OBJECTIVES: Estimate total incremental costs from second fracture for patients with closed hip, vertebral, and non-hip non-vertebral (NHNV) fractures in the commercially insured US population. METHODS: Patients with closed hip, vertebral, and NHNV fracture were identified in 2002-2008 MarketScan® Commercial Database. All patients were 50-64 years old at incident fracture and had data 12-month pre- and post-period from incident fracture. Cases experienced a subsequent fracture during the 12-month post-period with index date as the first subsequent fracture date. Controls had no subsequent fractures during the post-period; their index dates were randomly assigned based on the distribution of index dates of cases. All patients had 12-month post-period from index date and total costs were examined during the 12-month. Multivariate regressions controlled for demographic and clinical characteristics between cases and controls. Annual costs were projected to US commercially insured population in 2002-2008 based on projected number of patients with second fractures using weights derived from the Medical Expenditure Panel Survey. RESULTS: A total of 4752 hip, 10,080 vertebral, and 52,734 NHNV patients met the study criteria, with a mean age of 58 years and 63.9% women.  Average annual costs per person were $71,272 for cases vs. $20,828 for controls, $67,772 vs. $20,029 and $41,635 vs. $11,212 for the hip, vertebral, and NHNV cohort, respectively. Regression-adjusted incremental costs were $47,351, $43,238, and $23,852 for hip, vertebral, and NHNV fracture patients, respectively. The annual incremental costs associated with second fracture were projected to be $166.4 million, $199.2 million, and $468.8 million among patients 50-64 years old with initial hip, vertebral, and NHNV fracture in the US commercially insured population. CONCLUSIONS: There is substantial cost burden associated with second fracture on the US healthcare system.  Intervention for patients after their first fractures may help reduce the long-term economic and clinical burden associated with second fracture.