Purpose To assess the diagnostic value of apparent diffusion coefficients (ADCs) in spontaneous intracranial abscesses compared with those occurring after primary neurosurgery. Materials and Methods This retrospective comparative study was approved by the local institutional review board. The requirement to obtain written informed consent was waived. A total of 73 consecutive patients who underwent preoperative diffusion-weighted magnetic resonance (MR) imaging from February 2005 to May 2015 were divided into two cohorts depending on whether the abscess was identified after a primary neurosurgical procedure (n = 43) or was a spontaneous abscess (n = 30). Abscesses were assessed for ADC by two readers independently. ADCs were described as medians with interquartile range. The Mann-Whitney and χ(2) tests were used to compare ADCs between the two cohorts, and χ(2) automatic interaction detection analysis was used to classify the ADCs into categories according to the cohorts. Results The median ADC of postoperative abscesses was 1.34 × 10(-3) mm(2)/sec (interquartile range, 1.00-1.62 × 10(-3) mm(2)/sec), which was significantly higher than the median ADC of spontaneous abscesses, 0.68 × 10(-3) mm(2)/sec (interquartile range, 0.58-0.79 × 10(-3) mm(2)/sec; P < .001). Twenty four (83%) of the abscesses with ADCs less than 0.79 × 10(-3) mm(2)/sec were found to be spontaneous, while only six (27%) abscesses with ADCs between 0.79 and 1.33 × 10(-3) mm(2)/sec and no abscesses with ADCs greater than 1.33 × 10(-3) mm(2)/sec were spontaneous (P < .001). Conclusion Significantly higher ADCs were found in postoperative abscesses compared with those in spontaneous abscesses. Diffusion-weighted imaging with ADC mapping is not sufficient for excluding postoperative intracranial abscess and should not be used as the key diagnostic modality in this situation. (©) RSNA, 2016.