The association between bisphosphonate adherence in the first 12. months after therapy initiation and subsequent fracture risk was examined. Patients were identified from a large, commercially-insured population with integrated pharmacy and medical claims. Eligible patients were aged ≥ 45. years, were new to osteoporosis therapy (no osteoporosis medication claims in prior year) with first (index) bisphosphonate claim between 1/1/2005 and 4/30/2008, and had continuous insurance coverage for ≥ 12. months pre- and post-index. Patients with fracture claims ≤ 12-months post-index were excluded. Adherence was assessed using the medication possession ratio (MPR) over 12-months post-index (i.e., sum of days' supply dispensed divided by 365. days). Patients with a MPR > 0.8 were considered adherent. The follow-up period to assess incident fracture began at month 13. The analysis included 33,558 new bisphosphonate users with mean age (SD) 59.5 (9.3) years; 94.0% were female. Median MPR at 12. months was 0.61 for alendronate and risedronate; 0.58 for ibandronate. Proportionally more nonfracture patients (39.3%) had a MPR > 0.8 compared with fracture patients (34.9%, p< 0.001). In multivariate modeling of bisphosphonate users' experience, those with a MPR > 0.8 had a 14% lower risk of subsequent fracture than those with MPR < 0.5, after controlling for demographics, insurance type, select comorbidities, and other potential confounders (p= 0.0459). In a large, commercially-insured population, suboptimal adherence with bisphosphonate treatment was associated with increased fracture risk even after controlling for potential confounders. © 2011 Elsevier Inc.