Image quality in high-field intraoperative MRI (iMRI) is often influenced negatively by susceptibility artifacts. While routine sequences are rather robust, advanced imaging such as diffusion-weighted imaging (DWI) is very sensitive to susceptibility resulting in insufficient imaging data. This study aims to analyze intraoperatively acquired DWI to identify the main factors for susceptibility, to compare results with postoperative images and to identify technical aspects for improvement of intraoperative DWI. 100 patients with intraaxial lesions operated in a high-field iMRI were analyzed retrospectively for the quality of intraoperative DWI in comparison to the postoperative scan. General quality of the MR scan, individual diffusion restrictions, artifacts, and their causes were analyzed. Inclusion criteria were met in 78 patients, 124 diffusion restrictions were included in the comparative analysis. PPV and NPV for the detection of DWI changes intraoperatively were 0.94 and 0.56, respectively (SEN 0.94; SPE 0.56). Image quality was rated significantly (p < 0.0001) worse intraoperatively compared to the postoperative MRI. The main reasons for reduced image quality intraoperatively were air (64%) and artificial material (e.g., compress) (38%) in the resection cavity, as well as positioning of patient's head outside the MR's isocenter 37%. Analysis of surgical approaches showed that frontal craniotomies have the highest risk of limited image quality (40%), whereat better results (15% limited image quality) were seen for all other approaches (p = 0.059). Intraoperative DWI showed reliable results in this analysis. However, image-quality was limited severely in many cases leading to uncertainty in the interpretation. Susceptibility-causing factors might be prevented in many cases, if the surgical team is aware of them. The most important factors are good filling of the resection cavity with irrigation fluid, not placing artificial materials in the resection cavity and adequate positioning of patient's head according to the MR isocenter.