The recommended technique for breast diffusion-weighted imaging (DWI) acquisitions is not sufficiently standardized in clinical practice.To investigate the intraobserver and interobserver reproducibility of DWI measurements, diffusion-kurtosis imaging (DKI) parameters, and image quality evaluation in breast lesions between single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI).Prospective.A total of 295 women with 209 malignant and 86 benign breast lesions.A 3-T; fat-saturated T2-weighted MR imaging (T2WI); multi-b-value DWI with both ss-EPI and rs-EPI readouts; T1-weighted dynamic contrast-enhanced MRI (DCE-MRI).Mean kurtosis (MK), mean diffusion (MD), and apparent diffusion coefficient (ADC) values were measured for each lesion on ss-EPI and rs-EPI, respectively. Image quality was visually evaluated regarding image sharpness, geometric distortion, lesion conspicuity, visualization of anatomic structures, and overall quality. Quantitative and qualitative analyses were performed twice with a time interval of 2 weeks.Intraobserver and interobserver reproducibility were evaluated using intra-class correlation coefficients (ICC), within-subject coefficient of variation (wCV), and Bland-Altman plots.MK, MD, and ADC quantitative parameters for breast lesions showed excellent intraobserver and interobserver reproducibility, with ICCs >0.75 and wCV values ranging from 2.51% to 7.08% for both sequences. The wCV values in both intraobserver and interobserver measurements were higher in the ss-EPI sequence (3.63%-7.08%) than that of the rs-EPI sequence (2.51%-3.62%). The wCV values differed in subgroups with different histopathological types of lesions, breast density, lesion morphology, and lesion sizes, respectively. Furthermore, rs-EPI (ICCs, 0.76-0.97; wCV values, 2.41%-6.04%) had better intraobserver and interobserver reproducibility than ss-EPI (ICCs, 0.54-0.90; wCV values, 6.18%-13.69%) with regard to image quality.Compared to the ss-EPI, the rs-EPI sequence showed higher intraobserver and interobserver reproducibility for quantitative diffusion-related parameters and image quality assessments measured in breast DWI and DKI.2.Stage 2.© 2023 International Society for Magnetic Resonance in Medicine.