OBJECTIVE To assess the impact of elevated heart rate (HR) on the diagnostic accuracy and image quality of second-generation 320-detector computed tomography coronary angiography (320-CTCA). METHODS Consecutive patients with suspected coronary disease referred for invasive coronary angiography (ICA) were prospectively recruited and underwent 320-CTCA. Pre-scan beta-blockers were administered if native HR>80 bpm and post-scan cohorts stratified by traditional (HR ≤60 bpm) and elevated HR (61-80 bpm). A wider phase window was used for the elevated HR group (30-80%). 320-CTCA and ICA were analyzed by independent readers blinded to other data. Significant disease was defined as ≥50% visual stenosis on ICA. Uninterpretable segments by 320-CTCA were considered to be significant on an intention-to-diagnose principle. Image quality was assessed by 5-point Likert score. RESULTS Of 107 patients studied (1,662 segments), there was no significant difference in sensitivity, specificity, positive and negative predictive value between patients with HR ≤60 bpm (n=55) vs. HR 61-80 bpm (n=52): 97%, 88%, 95%, 94% vs. 100%, 88%, 95%, 100%; Receiver operator characteristic-area under the curve 0.93 vs. 0.94, P=0.82). Overall per-patient diagnostic accuracy was 96% in both groups with no significant difference in interpretable segments (Likert ≥2) or median radiation dose (2.4 mSv vs. 2.7 mSv, P=0.35). Only 4/1,662 (0.2%) segments were uninterpretable by motion artefact in the whole cohort. CONCLUSIONS In patients with HR >60 and up to 80bpm, second generation 320-CTCA provides comparably adequate diagnostic accuracy to HR ≤60 without significantly impacting upon overall segmental evaluability.