Advances in image reconstruction are necessary to decrease radiation exposure from coronary CT angiography (CCTA) further, but iterative reconstruction has been shown to degrade image quality at high levels. Deep-learning image reconstruction (DLIR) offers unique opportunities to overcome these limitations. The present study compared the impact of DLIR and adaptive statistical iterative reconstruction-Veo (ASiR-V) on quantitative and qualitative image parameters and the diagnostic accuracy of CCTA using invasive coronary angiography (ICA) as the standard of reference. This retrospective study includes 43 patients who underwent clinically indicated CCTA and ICA. Datasets were reconstructed with ASiR-V 70% (using standard SD and high-definition HD kernels) and with DLIR at different levels (i.e., medium M and high H). Image noise, image quality, and coronary luminal narrowing were evaluated by three blinded readers. Diagnostic accuracy was compared against ICA. Noise did not significantly differ between ASiR-V SD and DLIR-M (37 vs. 37 HU, p = 1.000), but was significantly lower in DLIR-H (30 HU, p < 0.001) and higher in ASiR-V HD (53 HU, p < 0.001). Image quality was higher for DLIR-M and DLIR-H (3.4–3.8 and 4.2–4.6) compared to ASiR-V SD and HD (2.1–2.7 and 1.8–2.2; p < 0.001), with DLIR-H yielding the highest image quality. Consistently across readers, no significant differences in sensitivity (88% vs. 92%; p = 0.453), specificity (73% vs. 73%; p = 0.583) and diagnostic accuracy (80% vs. 82%; p = 0.366) were found between ASiR-V HD and DLIR-H. DLIR significantly reduces noise in CCTA compared to ASiR-V, while yielding superior image quality at equal diagnostic accuracy. The present study evaluated the impact of deep-learning image reconstruction (DLIR) on noise, image quality, and diagnostic accuracy. In 43 patients who underwent clinically indicated coronary CT angiography and invasive coronary angiography, image quality was improved by up to 62% at similar noise levels. In addition, DLIR-H yielded the highest noise reduction (up to 43%) and best image quality (improvement of up to 138%). More importantly, sensitivity (92% vs. 88%), specificity (73% vs. 73%) and diagnostic accuracy (82% vs. 80%) of DLIR were at least non-inferior to ASiR-V.