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PURPOSE We investigated the impact of model-based iterative reconstruction (MBIR) on 320-detector row computed tomography angiography (CTA) in infants with complex congenital heart disease (CHD). METHODS Seventy infants with complex CHD who underwent 320-detector row CTA (40 boys and 30 girls; age range, 0-22 months; median age, 60 days) were retrospectively evaluated. First, the images were reconstructed by filtered back projection (FBP), hybrid iterative reconstruction (HIR), or MBIR in 20 cases, and variables were compared among the three iterative reconstruction methods (IR test). Second, the variables were compared between 25 cases scanned using HIR and 25 cases scanned using MBIR, with a 20 standard deviation noise level for both. Attenuation values and contrast-to-noise ratios (CNRs) of the great vessels and heart chambers were calculated. Total dose-length products were recorded for all patients (radiation dose: RD test). RESULTS In the IR test, the mean CNR values were 4.8±1.3 for FBP, 6.9±1.4 for HIR, and 8.2±1.7 for MBIR (P < 0.0001). The best subjective image qualities in the great vessels and heart chambers were obtained with MBIR. In RD testing, no significant differences between HIR and MBIR in image quality (CNR: HIR, 8.4±2.4; MBIR, 8.3±2.4) were observed. The effective dose was significantly lower for MBIR than for HIR (0.7±0.2 vs. 1.1±0.3 mSv; P < 0.001). CONCLUSION The MBIR algorithm significantly improved image quality and decreased radiation exposure in 320-row CTA of infants with complex CHD, providing an alternative to FBP or HIR that is both safer and produces better results.