We sought to evaluate the diagnostic accuracy of noninvasive coronary angiography using 320-detector row computed tomography, which provides 16-cm craniocaudal coverage in 350 ms and can image the entire coronary tree in a single heartbeat, representing a significant advance from previous-generation scanners. We evaluated 63 consecutive patients who underwent 320-detector row computed tomography and invasive coronary angiography for the investigation of suspected coronary artery disease. Patients with known coronary artery disease were excluded. Computed tomographic (CT) studies were assessed by 2 independent observers blinded to results of invasive coronary angiography. A single observer unaware of CT results assessed invasive coronary angiographic images quantitatively. All available coronary segments were included in the analysis, regardless of size or image quality. Lesions with >50% diameter stenoses were considered significant. Mean heart rate was 63 ± 7 beats/min, with 6 patients (10%) in atrial fibrillation during image acquisition. Thirty-three patients (52%) and 70 of 973 segments (7%) had significant coronary stenoses on invasive coronary angiogram. Seventeen segments (2%) were nondiagnostic on computed tomogram and were assumed to contain significant stenoses on an "intention-to-diagnose" analysis. Sensitivity, specificity, and positive and negative predictive values of computed tomography for detecting significant stenoses were 94%, 87%, 88%, and 93%, respectively, by patient (n = 63), 89%, 95%, 82%, and 97%, respectively, by artery (n = 260), and 87%, 97%, 73%, and 99%, respectively, by segment (n = 973). In conclusion, noninvasive 320-detector row CT coronary angiography provides high diagnostic accuracy across all coronary segments, regardless of size, cardiac rhythm, or image quality.