OBJECTIVES: End stage renal disease (ESRD) is associated with a substantial clinical and economic burden that impacts significantly on health-care systems. The objective of this study was to estimate the direct costs associated with ESRD in the Greek health care system. METHODS: A cost of illness analysis was performed using a Markov model to estimate the direct costs associated with the treatment of ESRD. Clinical inputs were derived from ERA-EDTA Registry 2004 Annual Report and published data of the renal replacement therapy (RRT) in Greece. The costs for hospital haemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and kidney transplantation (TX) were calculated. All costs were calculated from the perspective of the Greek health care system, in 2006 Euros. RESULTS: At the end of 2006, it was estimated that more than 11,000 patients were receiving RRT. The total economic burden of the Greek health care system for the RRT of these patients was estimated at more than 392.746 million Euros during 2006, almost 30% more than 2003, and represents 0.16% of the gross national product. The average weighted cost of RRT per patient year was 38,413 Euros. Although the cost of TX per patient year (after transplant surgery) was just 20,727 Euros, only 18.6% of the patients with ESRD received TX. CONCLUSION: The magnitude of the economical burden that the public insurance system pays for the treatment of ESRD in Greece is another reason for developing strategies to reduce the incidence of ESRD, as well as the cost of its treatment. Among the latter, an increase of kidney transplantations in national level seems to be a quite effective measure.