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Purpose Investigate the impact of acquisition time and reconstruction parameters on single‐photon emission computed tomography/computed tomography (SPECT/CT) image quality with the ultimate aim of finding the shortest possible acquisition time for clinical whole‐body SPECT/CT (WB‐SPECT/CT) while maintaining image quality Methods The National Electrical Manufacturers Association (NEMA) image quality measurements were performed on a SPECT/CT imaging system using a NEMA International Electrotechnical Commission (IEC) phantom with spherical inserts of varying diameter (10–37 mm), filled with 99mTc in activity sphere‐to‐background concentration ratio of 8.5:1. A gated acquisition was acquired and binned data were summed to simulate acquisitions of 15, 8, and 3 s per projection angle. Images were reconstructed on a Hermes (HERMES Medical Solutions AB, Stockholm, Sweden) workstation using eight subsets and between 4 and 24 iterations of the three‐dimensional (3D) ordered subset expectation maximization (OSEM) algorithm. Reconstructed images were post‐smoothed with 3D Gaussian filter ranging from 0 to 12 mm full‐width at half maximum (FWHM). Contrast recovery, background variability, and contrast‐to‐noise ratio were evaluated Results As expected, the spheres were more clearly defined as acquisition time and count statistics improved. The optimal iteration number and Gaussian filter were determined from the contrast recovery convergence and level of noise. Convergence of contrast recovery was observed at eight iterations while 12 iterations yielded stabilized values at all acquisition times. In addition, it was observed that applying 3D Gaussian filter of 8–12 mm FWHM suppressed the noise and mitigated Gibbs artifacts. Background variability was larger for small spheres than larger spheres and the noise decreased when acquisition time became longer. A contrast‐to‐noise ratio >5 was reached for the two smallest spheres of 10 and 13 mm at acquisition times of 8 s Conclusion Optimized reconstruction parameters preserved image quality with reduce acquisition time in present study. This study suggests an optimal protocol for clinical 99mTc SPECT/CT can be reached at 8 s per projection angle, with data reconstructed using 12 iterations and eight subset of the 3D OSEM algorithm and 8 mm Gaussian post‐filter.