OBJECTIVES: Ischemic Heart Disease (IHD) is the leading cause of death worldwide, including in Saudi Arabia.  Cost of illness (COI) studies aiming to explore the burden of IHD are missing in Saudi Arabia. Therefore, the objective of this study is to estimate the direct medical costs associated with IHD at Prince Sultan Cardiac Center (PSCC), a major Cardiac referral center in the country. METHODS: A prospective COI study was conducted from April 2009 to June 2009 from the PSCC perspective. All patients diagnosed or suspected having IHD at admission were included in the study. They were followed up till discharge or performing CABG or changing diagnosis. Clinical data were extracted from the patient computerized database and combined with the unit cost of services (medication, procedures, bed utilization) to calculate direct medical costs. RESULTS: A total of 205 patients were recruited and diagnosed with stable angina (SA) (47.8%), unstable angina (USA) (24.4%), STEMI (19.5%) and NSTEMI (8.3%). Most of the patients were male, Saudi, aged between 40-75 years. 87% of the patients had two or more co-morbidities and 32% of the patients were obese. The average cost is 40,164 SAR/patient (US$10,710). Medication contributed the lowest in the costs (3.2%). ACEI contributed only 0.17% in the total costs. Costs associated to SA, USA, NSTEMI and STEMI were respectively 33,991; 35,107; 46,585 and 58,877 SAR/patient. The lowest hospital length of stay was 6.5 days with SA. The average length of stay increased with the number of co-morbidities from 5.67 (no co-morbidity) to 11.25 (6 co-morbidities). CONCLUSIONS: The study shows that IHD is of high economic burden in the Kingdom. Among the 4 types of IHD studied, the resource consumption associated to SA was the lowest in terms of costs and patient hospital length of stay. Co-morbidities increased the hospital length of stay.