OBJECTIVES To analyze the financial impact of reimbursing everolimus, azathioprine and MMF in heart transplantation by Brazilian Ministry of Health. To review economic evaluations studies published to date regarding these three drugs. METHODS The economic impact was determined comparing the annual costs with drug and adjuvant therapy. The prices established by government for these drugs in renal transplantation were considered. Leaflet's recommendations were followed for everolimus and MMF dosages. The dosage of azathioprine was based on clinical trials. The average cyclosporine dosages were taken according to the respective treatment available in clinical trials. Cochrane, Pubmed and Medline databases were used for pharmacoeconomic studies research. RESULTS The most cost-saving therapy was found to be azathioprine, followed by everolimus, with the incremental annual cost of US$2862.81 (R$ 2.27/USD 1.00) compared to azathioprine. The third is MMF, showing US$704.69 of incremental cost compared to everolimus. According to the reviewed economic studies, everolimus is the most effective for the prevention/stabilization of CAV (cardiac allograft vasculopathy) and is associated with economic benefits due to its association with reduced hospitalization days due to Major Acute Cardiac Events (MACE). Both everolimus and MMF are more cost-effective than azathioprine in the first 6 months after heart transplantation, with everolimus presenting a more favorable ratio than MMF. CONCLUSIONS Azathioprine is the cheapest drug for prophylaxis of cardiac transplant rejection. However there are important economic studies assessing the cost benefit of treatment outcome that have to be considered. One of the most important aspect is the effectiveness of preventing CAV, the major cause of late morbity and mortality following heart transplantation. To date, re-transplantation remains the only definite treatment for severe CAV, but there are ethical, cost concerns and poorer outcomes compared to primary transplantation that appear to be hurdles to re-transplantation.