OBJECTIVE: As lipid-lowering therapy is likely to be long term and as many patients with hyperlipidemia are asymptomatic, adherence to HMG CoA Reductase Inhibitors (statins) may be of relevance to the cost effectiveness of these expensive agents. Therefore, rates of statin usage in the Irish community setting were established and effects on the incremental cost effectiveness ratios (ICERs) of individual statin drugs in both primary and secondary prevention of coronary heart disease (CHD) calculated. METHODS: Non-adherence rates were established for 4,948 patients prescribed statins over an 18-month period (Sept. 1999 to Feb. 2001) using a prescription-claims database. A Markov model investigating the cost effectiveness of statins, using Irish costs for medications and acute myocardial infarction (AMI) treatment, Irish mortality probabilities and outcomes for AMI and death from the 4S trial for secondary prevention and the WOSCOPs trial for primary prevention was adapted for these non-adherence rates. Changes in the discounted ICERs per quality adjusted life year (QALY) were calculated. RESULTS: Atorvastatin was the most cost-effective agent in both primary and secondary prevention of CHD followed by fluvatstatin, simvastatin and pravastatin. ICERs ranged from 1,172 to 3,900 Euro/QALY in secondary prevention, increasing to 2,388 and 7,508 Euro/QALY when non-adherence was factored. The effect in primary prevention was even more apparent. Discounted ICERs/QALY ranged from 17,668 Euro for atorvastatin to 38,459 Euro for pravastatin. Effects of non-adherence increased primary prevention ICERs to 24,663 and 57,494 Euro/QALY respectively. CONCLUSION: Non-adherence is rarely considered in pharmacoeconomic evaluation. However, this study illustrates that non-compliance can have a significant impact on the cost effectiveness of all statins in the Irish setting. This is likely to be the case for most expensive medications indicated over the long-term in all healthcare settings. Therefore, the effects of non-compliance should be considered before results from economic evaluation are used to influence prescription choice.