OBJECTIVES: Medication compliance is a significant factor contributing to the clinical- and cost-effectiveness of therapy. This study aimed to investigate the evidence on the overall cost of non-compliance with medication, taking osteoporosis therapy as an example. METHODS: The specific question addressed was “What are the direct medical healthcare costs of non-compliance and non-persistence in osteoporosis”. A Literature review was conducted to search for publications presenting work under the broad terms “costs”, “compliance/persistence” and “osteoporosis”. The databases searched were Medline, EMBASE, and the Cochrane Library. The listings were then appraised to identify those papers relevant to the study question and for inclusion in the evidence base. This evidence base was then investigated, in order to assess findings to answer the study question. RESULTS: In total, 52 papers were listed; four were relevant for inclusion. two of these articles were retrospective cohort studies and two were based on budget-impact models. Costs were presented as medical charges; medication possession ratio (MPR) and/or persistence rates were measures of non-compliance; osteoporosis medications included bisphosphonates and HRT. US Medical charges were 35% higher in non-compliers compared with compliers and total monthly charges were 76% higher. Based on modelling, persistence levels with bisphosphonates of <50% at 12 months results in almost 20,000 excess fractures over a 10 year period and £22M per annum fracture-related costs to the UK NHS. CONCLUSION: The evidence base in this area is limited. However, it indicates that medication non-compliance and failure to persist has substantial financial consequences within the field of osteoporosis management. This conclusion is consistent with the evidence available from both observation studies and modelling analyses in the US and UK healthcare systems. Further work is warranted to review other disease areas, and to further synthesise the data to provide an estimated aggregate of the international cost of medication non-compliance.