OBJECTIVES: Increasing real-life adherence to bisphosphonates therapy is important to achieve the clinical benefits of reducing fractures reported in randomized clinical trials (RCTs). The aim of this pharmacoeconomic analysis was to determine the cost-effectiveness of a pharmaceutical care intervention program in community pharmacies, aimed to increase bisphosphonates adherence for the prevention of osteoporotic fractures. METHODS: A decision analytical model was constructed with a time horizon of three years, discounting at 4.0% and 1.5% annually for costs and effects, respectively. A Dutch healthcare provider’s perspective was adopted. Adherence and efficacy data were gathered from a Dutch pharmaceutical care program in community pharmacies (the MeMO intervention). The association between bisphosphonate adherence and osteoporotic fractures was modelled using Dutch clinical studies. Recent and upcoming reimbursement policy changes in The Netherlands were modelled with a scenario of therapeutic substitution, characterized by drastically lower drug prices. RESULTS: Adherence to bisphosphonates therapy in The Netherlands was 68.3%. The pharmaceutical care intervention program increased bisphosphonates adherence to 83.9% (P<0.001). If the intervention program would be introduced nationwide in community pharmacies, 337 osteoporotic fractures would be prevented and 47 quality-adjusted life years (QALYs) would be gained. Additional medication and intervention costs were €1,738,000; the cost-savings due to reduced fractures were €998,000. The cost-effectiveness of the pharmaceutical care intervention was €16,000 per QALY. When drug prices decline following therapeutic substitution policies, the intervention will be cost-saving. CONCLUSIONS: Pharmaceutical care programs in community pharmacies, such as the MeMO intervention, can improve bisphosphonate adherence, resulting in a considerable number of osteoporotic fractures being prevented. Therapeutic substitution policies that lower drug prices will increase the cost-effectiveness of interventions that increase adherence. This study demonstrates the value of pharmaceutical care programs in community pharmacies to increase therapy adherence.