Background: Recently, multidetector computed tomography (MDCT) has been proposed as an accurate diagnostic tool to evaluate for coronary artery disease. However, the role of MDCT as part of the initial diagnostic for evaluating acute chest pain is less well established. Methods: We prospectively enrolled patients presenting with acute chest pain to the emergency department (ED) and risk stratified them based on the pretest probability for an acute coronary syndrome (ACS): (1) very low, (2) low, (3) intermediate, (4) high, and (5) very high or definite. After exclusion of very low and very high risk patients, 268 patients were randomized to either immediate 64-slice cardiac MDCT or a conventional diagnostic strategy. Number of admissions, ED and hospital length of stay (LOS), and major adverse cardiac events over 30 days of follow-up were compared between the strategies based on the pretest probability for ACS. Results: The number of patients ultimately diagnosed with an ACS did not differ between the 2 strategies. Emergency department LOS and total admissions were not different between strategies. Patients in the MDCT-based strategy had a decreased hospital LOS (P = .049) and fewer admissions deemed unnecessary (P = .007). Reductions in unnecessary admissions were more prominent in intermediate-risk patients (P = .015). None of the patients discharged from the ED in the MDCT-based strategy experienced major adverse cardiac events at follow-up. Conclusion: Use of an MDCT-based strategy in the ED as part of the initial diagnostic approach for patients presenting with acute chest pain is safe and efficiently reduces avoidable admissions in patients with an intermediate pretest probability for ACS.