This evaluation aimed to assess the economic performance of the Mediterranean diet for patients after a first acute myocardial infarction (AMI). A cost utility analysis using a Markov model was used to compare the Mediterranean diet to a prudent Western diet over a time frame of 10 years. After a systematic review of the literature, program effectiveness was based on the Lyon Diet Heart Study (605 patients, mean age 54 y, randomized to the Mediterranean diet delivered by a dietician and cardiologist, or a prudent Western diet). Costs were estimated in AU$ [and converted to US$ and Euros (euro)] based on the resource use to which published unit costs were applied. Cost and benefits were discounted at 5% per annum. The main outcome measure was cost per quality-adjusted life year (QALY) gained. Extensive 1-way sensitivity analyses were performed. The Mediterranean diet compared with a prudent Western diet was estimated to cost AU$1013 (US$703, euro579) per QALY gained per person. There was a mean gain in life years of 0.31/person and a gain in quality-adjusted life years of 0.40/person. Based on the published results from the Lyon Diet Heart Study and conservative assumptions, the Mediterranean diet is highly cost-effective for persons after a first AMI and represents an exceptional return on investment. Policy makers should strongly consider the generalizability of results to their own setting.