This prospective study evaluated the image quality and accuracy of coronary computed tomography angiography (CCTA) for diagnosing coronary artery disease (CAD) in patients with atrial fibrillation (AF), in which CCTA used adaptive iterative dose reduction (AIDR) with a low tube voltage and low concentration of isotonic contrast agent. Sixty-eight consecutive patients with AF and suspected CAD were equally and randomly apportioned to two groups and underwent CCTA. In the experimental group, the contrast agent was iodixanol (270 mg I/mL), patients were scanned with 100 kV, and reconstruction was by AIDR. In the conventional scanning (control) group, the contrast agent was iopromide (370 mg I/mL), patients were scanned with 120 kV, and reconstruction was by filtered back projection. The image quality, effective radiation dose (E), and total iodine intake of the groups were compared. Thirty-nine patients with coronary artery stenosis later were given invasive coronary angiography (ICA). The groups were similar with regard to mean CT value, noise, and signal-to-noise and contrast-to-noise ratios. The figure of merit of the experimental group was significantly higher than that of the control group, while the E and total iodine were significantly lower. Using ICA as the diagnostic reference, the groups shared similar sensitivity, specificity, and false positive and false negative rates for diagnosing coronary artery stenosis. For determining CAD in patients with AF, CCTA with isotonic low-concentration contrast agent and low-voltage scanning is a feasible alternative that improves accuracy and reduces radiation dose and iodine intake.