To compare the image quality of multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE-DWI) and single-shot echo-planar imaging (SS-EPI-DWI) techniques in uterine MRI.Eighty-eight eligible patients underwent MUSE-DWI and SS-EPI-DWI examinations simultaneously using a 3.0 T MRI system. Two radiologists independently performed quantitative and qualitative analysis of the two groups of images using a double-blind method. The weighted Kappa test was used to evaluate the interobserver agreement. Wilcoxon's rank sum test was used for qualitative parameters, and paired t-test was used for quantitative parameters. Spearman rank correlation analysis was used to obtained correlation between pathological results and mean apparent diffusion coefficient (ADC) value.The qualitative and quantitative analysis of the images by the two radiologists were in good or excellent agreement, with weighted kappa value ranging from 0.636 to 0.981. The scores of total subjective image quality (15.4 ± 0.99) and signal-to-noise ratio (158.99 ± 60.71) of MUSE-DWI were significantly higher than those of SS-EPI-DWI (12.93 ± 1.62 P < 0.001; 130.23 ± 48.29 P < 0.05). It effectively reduced image distortion and artifact, and had better lesion conspicuity. There was no significant difference in contrast-to-noise ratio score and average ADC values between the two DWI sequences. The average ADC values of the two DWI sequences were highest in the normal uterus group and lowest in the endometrial cancer group, with statistically significant differences among groups (P < 0.01). In addition, the average ADC values of the two DWI sequences were negatively correlated with the type of lesions, decreasing with the malignancy of the lesions (r = -0.805 P < 0.01, r = -0.815 P < 0.01).Compared to SS-EPI-DWI, MUSE-DWI can significantly reduce distortion, artifacts, and fuzziness in MRI of uterine lesions, which is more conducive to lesion detection.Copyright © 2024. Published by Elsevier Inc.