Background: Prone single photon emission computed tomography (SPECT) is suitable for evaluating the cardiac inferior wall as it suppresses attenuation artifacts from the diaphragm. The solid-state dedicated cardiac camera (D-SPECT) allows upright imaging, which can also be used to avoid attenuation artifacts from the diaphragm. We compared prone and upright imaging for inferior wall evaluation using 201TlCl myocardial perfusion SPECT. Methods: The study targeted 45 patients. The prone imaging group included 23 subjects who underwent additional prone imaging because supine imaging indicated that the inferior wall had reduced uptake. The upright imaging group included 22 subjects who had reduced uptake in the inferior wall during supine imaging in the past. Using the myocardial perfusion SPECT (MPS) stress images and Cardio Bull software, we created a polar map showing the incorporation of the radioisotope throughout the whole of the myocardium, and this polar map was then classified into 17 segments. The %uptake ratios of the inferior/anterior wall were calculated for the prone and upright acquisitions. These %uptake ratios used the ratio of the percentage uptake of each segment of the anterior wall to each segment of the inferior wall. In addition, six reviewers visually evaluated the uniformity within the inferior wall for both the prone and upright imaging. Results: There was a significant difference in the %uptake ratios between the prone and upright images in segment 4/1 (basal inferior/basal anterior; p<0.05), 11/12 (mid inferolateral/mid anterolateral; P < 0.001), and 15/13 (apical inferior/apical anterior; P < 0.05). There were no significant differences in the visual evaluations of the uniformity within the inferior wall between prone and upright MPS images. Conclusion: In comparison with upright imaging, prone imaging has a higher rate of suppression of attenuation artifacts from the diaphragm. However, the difference does not seem to affect the images visually. Therefore, upright and prone imaging can be used interchangeably to evaluate the inferior wall.