Emergency department presentations with chest pain are expensive and often unrelated to coronary artery disease (CAD). Coronary computed tomographic angiography (CTA) may allow earlier discharge of low-risk patients, resulting in cost savings. We modeled clinical and economic outcomes of diagnostic strategies in patients with chest pain and at low risk of CAD: exercise electrocardiography (ECG), stress single-photon emission computed tomography (SPECT), stress echocardiography, and a CTA strategy comprising an initial CTA scan with confirmatory SPECT for indeterminate results. Our results suggest that a 2-step diagnostic strategy of CTA with SPECT for intermediate scans is likely to be less costly and more effective for the diagnosis of a patient group at low risk of CAD and a prevalence of 2% to 30%. The CTA strategies were cost saving (lower costs, higher quality-adjusted life-years) compared with stress ECG, echocardiography, and SPECT. Confirming intermediate/indeterminate CTA scans with SPECT results in cost savings and quality-adjusted life-year gains due to reduced hospitalization of patients who returned false-positive initial CTA test. However, CTA may be associated with a higher event rate in negative patients than SPECT, and the diagnostic and prognostic information for the use of CTA in the emergency department is evolving. Large comparative, randomized, controlled trials of the different diagnostic strategies are needed to compare the long-term costs and consequences of each strategy in a population of defined low-risk patients in the emergency department.