Background. Recent studies have compared CTA to stress testing and MPI using older Na-I SPECT cameras and traditional rest-stress protocols, but are limited by often using optimized CTA protocols but suboptimal MPI methodology. We compared CTA to stress testing with modern SPECT MPI using high-efficiency CZT cameras and stress-first protocols in an ED population.Methods. In a retrospective, non-randomized study, all patients who underwent CTA or stress testing (ETT or Tc-99m sestamibi SPECT MPI) as part of their ED assessment in 2010-2011 driven by ED attending preference and equipment availability were evaluated for their disposition from the ED (admission vs discharge, length of time to disposition), subsequent visits to the ED and diagnostic testing (within 3 months), and radiation exposure. CTA was performed using a 64-slice scanner (GE Lightspeed VCT) and MPI was performed using a CZT SPECT camera (GE Discovery 530c). Data were obtained from prospectively acquired electronic medical records and effective doses were calculated from published conversion factors. A propensity-matched analysis was also used to compare outcomes in the two groups.Results. A total of 1,458 patients underwent testing in the ED with 192 CTAs and 1,266 stress tests (327 ETTs and 939 MPIs). The CTA patients were a lower-risk cohort based on age, risk factors, and known heart disease. A statistically similar proportion of patients was discharged directly from the ED in the stress testing group (82% vs 73%, P 5 .27), but their time to disposition was longer (11.0 ± 5 vs 20.5 ± 7 hours, P < .0001). There was no significant difference in cardiac return visits to the ED (5.7% CTA vs 4.3% stress testing, P 5 .50), but more patients had follow-up studies in the CTA cohort compared to stress testing (14% vs 7%, P 5 .001). The mean effective dose of 12.6 ± 8.6 mSv for the CTA group was higher (P < .0001) than 5.0 ± 4.1 mSv for the stress testing group (ETT and MPI). A propensity score-matched cohort showed similar results to the entire cohort.Conclusions. Stress testing with ETT, high-efficiency SPECT MPI, and stress-only protocols had a significantly lower patient radiation dose and less follow-up diagnostic testing than CTA with similar cardiac return visits. CTA had a shorter time to disposition, but there was a trend toward more revascularization than with stress testing. (J Nucl Cardiol 2014;21:305-18.)