Novel DWI sequences used for prostate MRI may allow for reduced acquisition time while maintaining image quality. In diagonal SS-EPI DWI (dDWI), the gradients are switched on simultaneously, to maximum amplitude at the highest b-value, which leads to shorter TE compared to standard 3-scan-trace DWI (tDWI). In addition, dDWI is expected to exhibit better image sharpness, since it uses only one gradient scheme and is therefore less sensitive to differences in eddy currents between gradient schemes. dDWI measures diffusion in one direction (the net gradient direction) as opposed to 3 directions tDWI and is therefore mainly applicable in tissues in which diffusion is considered isotropic. dDWI has been used previously in soft tissue tumors (1) and spine (2). We hypothesized that dDWI allows for similar image quality with similar ADC quantification in a shorter acquisition time compared to tDWI. The aim of our study was to compare dDWI to standard tDWI of the prostate in terms of image quality and quantitative ADC measurement. 24 consecutive men (mean age 63y) with suspected prostate cancer underwent 3T MRI (Siemens Skyra) of the prostate including tDWI and dDWI using b-values 50, 1000 and 1600 s/mm², FOV 250x250 mm², matrix 114x114, slice thickness 3 mm, 39 slices, TR/TE 8200/69 ms for tDWI and 9300/66 ms for dDWI, averages 1/5/10 in tDWI vs. 2/8/14 for dDWI, average acquisition time 6:21 min for tDWI vs. 4:17 min for dDWI. A higher number of averages was chosen for dDWI to compensate for the loss in SNR in dDWI. Two independent observers evaluated image quality (sharpness, distortion, artifacts and overall quality) on a 5-point scale, ranging from nondiagnostic (1) to excellent (5). ROIs were placed on transitional zone (TZ) and peripheral zone (PZ). Normalized SNR (nSNR) was calculated by dividing mean signal intensity (SI) by SD of SI in the ROI (3). ADC was measured on both sequences in PZ and TZ. Data was compared between the 2 sequences using paired Wilcoxon signed rank tests. Coefficients of variations (CV) between ADC measurements were calculated.Initial results are presented here. Representative images and ADC maps from tDWI and dDWI in the same patient are shown in Fig. 1. Table 1 shows the results from quantitative measurements of SNR and ADC in PZ and TZ. nSNR was significantly lower in PZ at b1600 and in TZ at b1000 and b1600 for the dDWI. Mean ADC was significantly higher in TZ with dDWI, while no differences were found for PZ. Reproducibility between sequences was excellent (mean CV 3.1±3.0% and 2.7±1.9% for PZ and TZ, respectively). Image quality results are provided for one observer (Table 2). Significantly fewer artifacts were observed in the dDWI, while the other image quality scores were similar. These initial results demonstrate the potential of dDWI in providing substantial reduction in acquisition time (40%) while maintaining adequate image quality and providing equivalent ADC values in non-tumor tissue. Next step will be to assess differences in tumor detection between tDWI and dDWI and to assess ADC reproducibility in tumor tissue.