Purpose <p>To evaluate the efficacy of deep learning reconstruction (DLR) in diffusion-weighted imaging (DWI) with single-shot echo-planar imaging (SSEPI) for endometrial cancer, compared to multiplexed sensitivity-encoding (MUSE) DWI.</p> Methods <p>We retrospectively reviewed 31 women with surgically confirmed endometrial cancer who underwent preoperative pelvic magnetic resonance imaging (MRI) including DWI. Qualitative analysis including overall image quality, susceptibility artifacts, sharpness of the uterine edge, and lesion conspicuity were compared among conventional SSEPI (SSEPI-C), SSEPI with DLR (SSEPI-DL), and MUSE using the Friedman’s test. Quantitative analysis including the apparent diffusion coefficient (ADC) values, noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also compared among three DWI sequences using the Friedman’s test. In addition, the diagnostic accuracy for deep myometrial invasion was compared to three DWI sequences using Cochran’s Q test.</p> Results <p>The scores of overall image quality, sharpness of the uterine edge, and lesion conspicuity in SSEPI-DL were higher than SSEPI-C (<i>p</i> &lt; 0.001) with no significant difference compared to MUSE (<i>p</i> &gt; 0.05). Noise in SSEPI-DL was lower than SSEPI-C (<i>p</i> &lt; 0.001), with no significant difference compared to MUSE (<i>p</i> &gt; 0.05). SNR and CNR in SSEPI-DL were also superior to SSEPI-C (<i>p</i> &lt; 0.001), and comparable to MUSE (<i>p</i> &gt; 0.05). The diagnostic accuracy for detecting deep myometrial invasion showed no significant difference among SSEPI-C, SSEPI-DL and MUSE (<i>p</i> &gt; 0.05).</p> Conclusion <p>DLR improves the image quality of DWI in endometrial cancer, demonstrating image quality equivalent to that of SSEPI-DL and MUSE. SSEPI-DL can be an alternative to MUSE in female pelvic MRI, with the benefit of significantly shortened scan time.</p> Graphical Abstract <p></p>