Objective: To compare the enhancement of the pulmonary and aortic vasculature between a biphasic injection 64-slice, a single-phase injection 16-slice, and a single-phase injection 10-slice multidetector computed tomographic (CT) angiography (CTA) protocols. Methods: With institutional review board approval and Health Insurance Portability and Accountability Act compliance, 50 patients (16 men, 34 women; mean age, 51.5 years; range, 30-75 years) with atypical chest pain from the emergency department were scanned using a triple rule-out protocol on a 64-slice CT scanner. Pulmonary enhancement was compared with 50 patients (21 men, 29 women; mean age, 65.6 years; range, 38-90 years) imaged with a single-phase 16-slice pulmonary angiography protocol. Aortic enhancement was compared with 24 patients (12 men, 12 women; mean age, 66.1; range, 34-92 years) who were imaged with a 16-slice aortic dissection CTA protocol and to 25 patients (15 men, 10 women; mean age, 50.8 years; range, 20-83 years) imaged with a 10-slice aortic dissection CTA protocol. A 2-tailed Student t test or sign test was used to assess significant differences from a vascular attenuation cutoff value of 250 Hounsfield units (HU). Results: Individual mean pulmonary arterial and aortic attenuation values were statistically significantly less than 250 HU for the 16- and 10-slice protocols and statistically significantly more than 250 HU for the 64-slice protocols (P < 0.05). Mean pooled pulmonary attenuation values were more than 250 HU in 18% (9/50) of the 16-slice and in 93% (39/42) of the 64-slice protocols. Mean pooled aortic attenuation values were more than 250 HU in 18.4% (9/49) of the 10- and 16- and in 100% (42/42) of the 64-slice protocols. Conclusions: The triple rule-out 64-slice biphasic injection breath hold CTA protocol provides significantly higher attenuation of aortic and pulmonary vasculature compared with our current 10- and 16-slice protocols.