Purpose To investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis over oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in patients with glioblastoma and the correlation between ADC parameters and MGMT status. Materials and Methods This retrospective study was approved by institutional review board, and informed consent was waived. A total of 112 patients with glioblastoma were divided into training (74 patients) and test (38 patients) sets. Overall survival (OS) and progression-free survival (PFS) was analyzed with ADC parameters, MGMT status, and other clinical factors. Multivariate Cox regression models with and without ADC parameters were constructed. Model performance was assessed with c index and receiver operating characteristic curve analyses for 12- and 16-month OS and 12-month PFS in the training set and validated in the test set. ADC parameters were compared according to MGMT status for the entire cohort. Results By using ADC parameters, the c indices and diagnostic accuracies for 12- and 16-month OS and 12-month PFS in the models showed significant improvement, with the exception of c indices in the models for PFS (P < .05 for all) in the training set. In the test set, the diagnostic accuracy was improved by using ADC parameters and was significant, with the 25th and 50th percentiles of ADC for 16-month OS (P = .040 and P = .047) and the 25th percentile of ADC for 12-month PFS (P = .026). No significant correlation was found between ADC parameters and MGMT status. Conclusion ADC histogram analysis had incremental prognostic value over MGMT promoter methylation status in patients with glioblastoma. (©) RSNA, 2016 Online supplemental material is available for this article.