Background: Cadmium-zinc-telluride (CZT) solid-state detectors have been recently introduced into the field of myocardial perfusion imaging. The aim of this study was to prospectively compare the diagnostic performance of the CZT high-speed gamma camera (Discovery NM 530c) with that of the standard 3-head gamma camera in the same group of patients. Methods and Results: The study group consisted of 150 consecutive patients who underwent a 1-day stress-rest ^99mTc-sestamibi or tetrofosmin imaging protocol. Image acquisition was performed first on a standard gamma camera with a 15-min scan time each for stress and for rest. All scans were immediately repeated on a CZT camera with a 5-min scan time for stress and a 3-min scan time for rest, using list mode. The correlations between the CZT camera and the standard camera for perfusion and function analyses were strong within narrow Bland-Altman limits of agreement. Using list mode analysis, image quality for stress was rated as good or excellent in 97% of the 3-min scans, and in 100% of the ≥4-min scans. For CZT scans at rest, similarly, image quality was rated as good or excellent in 94% of the 1-min scans, and in 100% of the ≥2-min scans. Conclusions: The novel CZT camera provides excellent image quality, which is equivalent to standard myocardial single-photon emission computed tomography, despite a short scan time of less than half of the standard time.  (Circ J 2013; 77: 1009–1017)