Background: Myocardial perfusion SPECT (MPS) traditionally requires the patient to be in the supine position, but diaphragmatic attenuation of the inferior wall reduces test specificity. The aim of this study was to assess the feasibility of combined MPS in the supine and prone positions using a novel cadmium zinc telluride (CZT) camera. Methods and Results: A total of 276 consecutive patients with suspected/known coronary artery disease (CAD) who underwent single-day ^99mTc-tetrofosmin or ^99mTc-sestamibi stress/rest CZT SPECT, were enrolled in the study. Seventy-six underwent coronary angiography. Five-minute scan in the supine (S) position and thereafter in the prone (P) position produced images that were visually interpreted to obtain summed stress (SSS) and rest (SRS) scores. A combined stress score (C-SSS) was calculated by grouping anterior perfusion defects observed during supine imaging with inferior half segments observed during prone imaging. The SSS for the supine, prone, and combined protocols were 9±8, 7±8, and 7±8, respectively (P<0.0001). The SRS were 5±8, 4±7, and 6±7, respectively (P=0.005). The area under the ROC curve for the S-SSS, P-SSS, and C-SSS scores was 0.815 (95% CI: 0.713–0.917), 0.813 (0.711–0.914), and 0.872 (0.783–0.961), respectively. Corresponding sensitivities and specificities for detecting CAD were 87% and 50%, 80% and 77%, and 85% and 82%, respectively. C-SSS had significantly better specificity and accuracy than S-SSS (P<0.05). Conclusions: Combined imaging with a CZT camera is suitable for routine clinical MPS and provides greater diagnostic accuracy than supine imaging alone.  (Circ J 2014; 78: 1169–1175)