We investigated the ability of echo-planar imaging with L1-regularized iterative sensitivity encoding-based diffusion-weighted imaging (DWI) to improve the image quality and reduce the scanning time in prostate magnetic resonance imaging. We retrospectively analyzed 109 cases of prostate magnetic resonance imaging. We compared variables in the quantitative and qualitative assessments among 3 imaging groups: conventional parallel imaging-based DWI (PI-DWI) with an acquisition time of 3 minutes 15 seconds; echo-planar imaging with L1-regularized iterative sensitivity encoding-based DWI (L1-DWI) with a normal acquisition time (L1-DWI NEX12 ) of 3 minutes 15 seconds; and L1-DWI with a half acquisition time (L1-DWI NEX6 ) of 1 minute 45 seconds. As a quantitative assessment, the signal-to-noise ratio (SNR) of DWI (SNR-DWI), the contrast-to-noise ratio (CNR) of DWI (CNR-DWI), and the CNR of apparent diffusion coefficient were measured. As a qualitative assessment, the image quality and visual detectability of prostate carcinoma were evaluated. In the quantitative analysis, L1-DWI NEX12 showed significantly higher SNR-DWI than PI-DWI (P = .0058) and L1-DWI NEX6 (P < .0001). In the qualitative analysis, the image quality score for L1-DWI NEX12 was significantly higher than those of PI-DWI and L1-DWI NEX6 . A non-inferiority assessment demonstrated that L1-DWI NEX6 was non-inferior to PI-DWI in terms of both quantitative CNR-DWI and qualitative grading of image quality with a <20% inferior margin. L1-DWI successfully demonstrated a reduced scanning time while maintaining good image quality. Abbreviations: ADC = apparent diffusion coefficient, CI = confidence intervals, CNR = contrast-to-noise ratio, DWI = diffusionweighted imaging, EPI = echo-planar imaging, FOV = field of view, L1-DWI = L1-regularized iterative SENSE-based DWI, L1-DWI NEX12 = L1-DWI with normal acquisition time, L1-DWI NEX6 = L1-DWI with half acquisition time, mp-MRI = multiparametric magnetic resonance imaging, PCa = prostate carcinoma, PI = parallel imaging, PI-DWI = PI-based DWI, PI-RADS = prostate imaging reporting and data system, ROI = region of interest, SENSE = sensitivity encoding, SNR = signal-to-noise ratio, ssEPI = single-shot spin-echo echo-planar imaging sequence, T2WI = T2-weighted image.