© 2015 All rights reserved: reproduction in whole or part not permitted. Purpose: In clinical trials, bisphosphonate therapy reduces but does not eliminate the risk of fracture. The objective of this retrospective observational study was to examine fracture rates among women who were adherent to bisphosphonate therapy for at least 1 year. Methods: We studied outcomes for women ≥50 years old who received their first osteoporosis therapy as an oral bisphosphonate during 2002-2008 and were enrolled in a large claims database for ≥3 consecutive years, including a baseline year before and 2 years after the index prescription (thus, the full study period was 2001-2010). Adherence during the first year of therapy was defined as a medication possession ratio (MPR) ≥80% (total number of days supply/365 days×100). Results: Of the 62,446 women who met the eligibility criteria, 26,852 (43%) had an MPR 80% for osteoporosis therapy during year 1. In year 2, the fracture rate was 52/1000 patient-years. Fragility fractures were recorded for 1292 patients (4.8%) during the baseline year (before initiating therapy); for 1051 patients (3.9%) during year 1 (adherence year); and for 871 patients (3.2%) during year 2. Significant predictors of fracture in year 2 were older age, higher comorbidity score, comorbid inflammatory joint disease, and prior fragility fracture during the baseline year or first year of treatment. The primary limitation of these results is the scope of the claims database, which did not provide information on bone mineral density, supplemental use of calcium or vitamin D, or reasons for initiating oral bisphosphonates. Conclusions: Despite being adherent to bisphosphonate treatment for 1 year, 3.2% of women experienced a fracture in the subsequent year. These results suggest an unmet need in patients with osteoporosis and an opportunity for newer therapies to help address this need.