Myocardial perfusion single photon emission computed tomography (SPECT) is invaluable diagnostic and prognostic tool in assessment of patients with coronary artery disease. Objective: The aim of the study was to look at the impact of different acquisition parameters and their quantitative influence on the quality of cardiac SPECT data in terms of contrast improvement, signal to noise ratio and contrast-to-noise ratio. Materials and Methods: A number of clinically relevant phantoms have been prepared and different acquisition parameters were implemented. These parameters were namely number of projections, time per projection, acquisition mode (S&S continuous, continuous rotation and conventional step and shot), rotation type, detectors configuration and single or dual detectors.Data evaluations were made using image contrast, signal to noise ratio, and contrast to noise ratio. Results: Time of projection showed an improvement in the figures of merit investigated as the time is increased. A time of 15 sec has reasonably provided comparable results when compared to 30 sec for NAC data set. When data were corrected for attenuation, longer acquisition time yielded the best image quality results. In terms of number of projections, data acquired with 64 projections were superior in all quantitative metrics. The acquisition mode results however were heavily dependent on whether AC or NAC was applied. When circular orbit was studied versus noncircular obit, most of image quality metrics were in favor of the noncircular rotation mode.An angular configuration of 76 degree was superior in most image quality aspects but some differences were noticed in AC and NAC data sets versus the 90 degree configuration. Data acquisition with one detector head was comparable but sometimes better than results obtained with dual head acquisitions. Conclusion: Image acquisition parameters are key elements of better diagnostic and improvedimage quality in myocardial perfusion SPECT imaging. Optimization of the acquisition parameters is a critical process especially when considered for every individual patient. We therefore recommend an on-site specific acquisition parameters might be the best approach to follow in routine activities provided substantial and several phantom and clinical trials.