Objectives: Medication nonadherence is common for osteoporosis, but its consequences have not been well described. This study aimed to quantify the clinical and economic impacts of poor adherence and to evaluate the potential cost-effectiveness of improving patient adherence by using hypothetical behavioral interventions. Methods: A previously validated Markov microsimulation model was adapted to the Irish setting to estimate lifetime costs and outcomes (fractures and quality-adjusted life-year [QALY]) for three adherence scenarios: no treatment, real-world adherence, and full adherence over 3 years. The real-world scenario employed adherence and persistence data from the Irish Health Services Executive-Primary Care Reimbursement Services pharmacy claims database. We also investigated the cost-effectiveness of hypothetical behavioral interventions to improve medication adherence (according to their cost and effect on adherence). Results: The number of fractures prevented and the QALY gain obtained at real-world adherence levels represented only 57% and 56% of those expected with full adherence, respectively. The costs per QALY gained of real-world adherence and of full adherence compared with no treatment were estimated at (sic)11,834 and (sic)6,341, respectively. An intervention to improve adherence by 25% would result in an incremental cost-effectiveness ratio of (sic)11,511 per QALY and (sic)54,182 per QALY, compared with real-world adherence, if the intervention cost an additional (sic)50 and (sic)100 per year, respectively. Discussion: Poor adherence with osteoporosis medications results in around a 50% reduction in the potential benefits observed in clinical trials and a doubling of the cost per QALY gained from these medications. Depending on their costs and outcomes, programs to improve adherence have the potential to be an efficient use of resources.