Background: Scarcity of prospective medication non-adherence cost measurements for the Australian population with no directly measured estimates makes determining the burden medication non-adherence places on the Australian health care system difficult. This study aims to indirectly estimate the national cost of medication non-adherence in Australia comparing the cost prior to and following a community pharmacy-led intervention. Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n=11,257 on rosuvastatin, n=6,797 on irbesartan and n=2,281 on desvenlafaxine) was analyzed and average adherence rate determined through calculation of PDC. Included patients received a pharmacist-led medication adherence intervention and had twelve months dispensing records; six months before and six months after the intervention. The national cost estimate of medication non-adherence in hypertension, dyslipidemia and depression pre-and post-intervention was determined through utilization of disease prevalence and comorbidity, non-adherence rates and per patient disease-specific adherence-related costs. Results: The total national cost of medication non-adherence across three prevalent conditions, hypertension, dyslipidemia and depression was $10.4 billion equating to $517 per adult. Following enrollment in the pharmacist-led intervention medication non-adherence costs per adult decreased $95 saving the Australian health care system and patients $1.9 billion annually. Conclusion: In the absence of a directly measured national cost of medication non-adherence, this estimate demonstrates that pharmacists are ideally placed to improve patient adherence and reduce financial burden placed on the health care system due to non-adherence. Funding of medication adherence programs should be considered by policy and decision makers to ease the current burden and improve patient health outcomes moving forward.@en