Recently published American Heart Association/American College of Cardiology guidelines suggest that multidetector computed tomography (MDCT) may be appropriate for investigating acute chest pain (ACP). Only a few small studies have evaluated the use of MDCT in ACP, where it was not part of routine investigation. We sought to evaluate the routine use of MDCT in a large cohort of patients presenting with ACP in a real-world setting. We studied 785 consecutive patients with ACP who underwent evaluation by MDCT or myocardial perfusion scintigraphy after an observation period of > or = 12 hours. Patients with findings suggestive of significant coronary artery disease (CAD) were referred to coronary angiography. Forty-two patients were hospitalized due to evidence of myocardial ischemia and 44 patients were discharged after the observation period. Of the remaining 699 patients, 340 underwent MDCT and 359 myocardial perfusion scintigraphy. In 22 patients (7%) multidetector computed tomogram showed significant CAD and in 32 (9%) patients myocardial perfusion scintigram showed significant ischemia. Significant CAD was confirmed by coronary angiography in 65% and 60%, respectively. Multidetector computed tomogram was nondiagnostic in 31 patients (9%). Extracardiac findings that might be related to ACP and/or necessitated further investigation were demonstrated by multidetector computed tomogram in 71 patients (21%). During 3-month follow-up, 1 patient (0.3%) with negative multidetector computed tomographic and 9 (3%) with negative myocardial perfusion scintigraphic findings developed an acute coronary syndrome or died. Rehospitalization, due to recurrent chest pain, occurred in 9 patients (3.3%) and 21 patients (7.2%), respectively. In conclusion, MDCT could be an appropriate alternative to traditional noninvasive techniques for investigating ACP.