Diagnostic strategies for coronary artery disease are diverse and include ① exercise EKG to coronary angiography, ② myocardial SPECT to coronary angiography, ③ dobutamine or exercise echocardiography to coronary angiography, and ④ direct coronary angiography. Cost-effectiveness analysis can be performed considering ① that the cost should include the costs of the diagnostic tests themselves, the cost of not-diagnosing the patients, the final test costs on false positive patients, and the cost to treat complications and ② that the effect should include quality-adjusted life year (QALY) with the fraction of proper diagnosis influenced by the diagnostic performance of the initial non-invasive tests. Based on the prior cost-effectiveness analysis, the pre-test likelihood affected most of the cost-effectiveness of a diagnostic strategy. Direct angiography was most cost-effective when the pre-test likelihood was high (>60%), while SPECT with or without a prior exercise EKG to angiography was most cost-effective when the pre-test likelihood was intermediate or low. Compared to stress echocardiography, stress myocardial SPECT was more cost-effective when the likelihood was moderate or high. While the prognostic significance of negative (including false-negative) cases was important to maintain cost-effectiveness of a strategy, myocardial SPECT to coronary angiography was the most cost-effective method to diagnose coronary artery disease.