The relationship between high adherence to oral bisphosphonates and the risk of different types of fractures has not been well studied among adults of different ages. Using claims data from a large U.S. health care organization, we quantified adherence after initiating bisphosphonate therapy using the medication possession ratio (MPR) and identified fractures. Cox proportional hazards models were used to evaluate the rate of fracture among nonadherent persons (MPR < 50%) compared with highly adherent persons (MPR >or= 80%) across several age strata and a variety of types of clinical fractures. In conjunction with fracture incidence rates among the nonadherent, these estimates were used to compute the number needed to treat with high adherence to prevent one fracture, by age and fracture type. Among 101,038 new bisphosphonate users, the proportion of persons with high adherence at 1, 2, and 3 yr was 44%, 39%, and 35%, respectively. Among 65- to 78-yr-old persons with a physician diagnosis of osteoporosis, the crude and adjusted rate of hip fracture among the nonadherent was 1.96 (95% CI, 1.48-2.60) and 1.74 (95% CI, 1.30-2.31), respectively, resulting in a number needed to treat with high adherence to prevent one hip fracture of 107. The impact of high adherence was substantially less for other types of fractures and for younger persons. Analysis of adherence in a non-time-dependent fashion artifactually magnified differences in fracture rates between adherent and nonadherent persons. The antifracture effectiveness associated with high adherence to oral bisphosphonates varied substantially by age and fracture type. These results provide estimates of absolute fracture effectiveness across age subgroups and fracture types that have been minimally evaluated in clinical trials and may be useful for future cost-effectiveness studies.