The purpose of this work was to assess the feasibility of acquisition time reduction in MPI-SPECT imaging using deep leering techniques through two main approaches, namely reduction of the acquisition time per projection and reduction of the number of angular projections.SPECT imaging was performed using a fixed 90° angle dedicated dual-head cardiac SPECT camera. This study included a prospective cohort of 363 patients with various clinical indications (normal, ischemia, and infarct) referred for MPI-SPECT. For each patient, 32 projections for 20 seconds per projection were acquired using a step and shoot protocol from the right anterior oblique to the left posterior oblique view. SPECT projection data were reconstructed using the OSEM algorithm (6 iterations, 4 subsets, Butterworth post-reconstruction filter). For each patient, four different datasets were generated, namely full time (20 seconds) projections (FT), half-time (10 seconds) acquisition per projection (HT), 32 full projections (FP), and 16 half projections (HP). The image-to-image transformation via the residual network was implemented to predict FT from HT and predict FP from HP images in the projection domain. Qualitative and quantitative evaluations of the proposed framework was performed using a tenfold cross validation scheme using the root mean square error (RMSE), absolute relative error (ARE), structural similarity index, peak signal-to-noise ratio (PSNR) metrics, and clinical quantitative parameters.The results demonstrated that the predicted FT had better image quality than the predicted FP images. Among the generated images, predicted FT images resulted in the lowest error metrics (RMSE = 6.8 ± 2.7, ARE = 3.1 ± 1.1%) and highest similarity index and signal-to-noise ratio (SSIM = 0.97 ± 1.1, PSNR = 36.0 ± 1.4). The highest error metrics (RMSE = 32.8 ± 12.8, ARE = 16.2 ± 4.9%) and the lowest similarity and signal-to-noise ratio (SSIM = 0.93 ± 2.6, PSNR = 31.7 ± 2.9) were observed for HT images. The RMSE decreased significantly (P value < .05) for predicted FT (8.0 ± 3.6) relative to predicted FP (6.8 ± 2.7).Reducing the acquisition time per projection significantly increased the error metrics. The deep neural network effectively recovers image quality and reduces bias in quantification metrics. Further research should be undertaken to explore the impact of time reduction in gated MPI-SPECT.