Background: Cost-effectiveness is an increasingly important factor in the choice of a test or therapy., Objective: To assess the cost-effectiveness of various methods routinely used for the diagnosis of stable coronary disease in Portugal., Methods: Seven diagnostic strategies were assessed. The cost-effectiveness of each strategy was defined as the cost per correct diagnosis (inclusion or exclusion of obstructive coronary artery disease) in a symptomatic patient. The cost and effectiveness of each method were assessed using Bayesian inference and decision-making tree analyses, with the pretest likelihood of disease ranging from 10% to 90%., Results: The cost-effectiveness of diagnostic strategies was strongly dependent on the pretest likelihood of disease. In patients with a pretest likelihood of disease of ≤50%, the diagnostic algorithms, which include cardiac computed tomography angiography, were the most cost-effective. In these patients, depending on the pretest likelihood of disease and the willingness to pay for an additional correct diagnosis, computed tomography angiography may be used as a frontline test or reserved for patients with positive/inconclusive ergometric test results or a calcium score of >0. In patients with a pretest likelihood of disease of ≥ 60%, up-front invasive coronary angiography appears to be the most cost-effective strategy., Conclusions: Diagnostic algorithms that include cardiac computed tomography angiography are the most cost-effective in symptomatic patients with suspected stable coronary artery disease and a pretest likelihood of disease of ≤50%. In high-risk patients (pretest likelihood of disease ≥ 60%), up-front invasive coronary angiography appears to be the most cost-effective strategy. In all pretest likelihoods of disease, strategies based on ischemia appear to be more expensive and less effective compared with those based on anatomical tests.