Using a computer simulation model, we determined that an intervention aimed at improving the management of glucocorticoid-induced osteoporosis is likely to be cost-effective to third-party health insurers only if it focuses on individuals with very high fracture risk and the proportion of prescriptions for generic bisphosphonates increases substantially. Introduction: The purpose of this study is to determine whether an evidence implementation program (intervention) focused on increasing appropriate management of glucocorticoid-induced osteoporosis (GIOP) might be costeffective compared with current practice (no intervention) from the perspective of a third-party health insurer. Methods: We developed a Markov microsimulation model to determine the cost-effectiveness of the intervention. The hypothetical patient cohort was of current chronic glucocorticoid users 50-65 years old and 70% female. Model parameters were derived from published literature, and sensitivity analyses were performed. Results: The intervention resulted in incremental costeffectiveness ratios (ICERs) of $298,000 per quality adjusted life year (QALY) and $206,000 per hip fracture averted. If the cohort's baseline risk of fracture was increased by 50% (10-year cumulative incidence of hip fracture of 14%), the ICERs improved significantly: $105,000 per QALY and $137,000 per hip fracture averted. The ICERs improved significantly if the proportion of prescriptions for generic bisphosphonates was increased to 75%, with $113,000 per QALY and $77,900 per hip fracture averted. Conclusions: Evidence implementation programs for the management of GIOP are likely to be cost-effective to third-party health insurers only if they are targeted at individuals with a very high risk of fracture and the proportion of prescriptions for less expensive generic bisphosphonates increases substantially. © International Osteoporosis Foundation and National Osteoporosis Foundation 2009.