Magnetic resonance imaging reveals heterogeneous regions within high-grade gliomas, such as a contrast-enhanced rim, a necrotic core, and non-contrast-enhanced abnormalities. It is unclear which of these regions best describes tumor aggressiveness. We hypothesized that the vascular leakage volume, reflecting disorganized angiogenesis typical of glioblastoma, would be a strong predictor of clinical outcome. The FLAIR tumor volume, post-gadolinium T1 tumor volume, tumor vascular leakage volume determined by dynamic contrast-enhanced imaging, and volume of the contrast-enhanced rim seen on post-gadolinium T1-weighted images were defined for 20 patients about to undergo treatment for newly diagnosed high-grade gliomas. The potential for imaging characteristics to improve prediction of survival and time to progression over clinical variables was tested by using Cox regression analysis. Single-variable Cox regression analysis of each of the four tumor subvolumes revealed that the vascular leakage volume was the only significant predictor of survival. When the joint effect of clinical variables and the vascular leakage volume were tested for prediction of survival, only the age and the vascular leakage volume were selected as significant predictors. However, when time to progression was tested as a dependent variable, both the vascular leakage volume and the vascular permeability were selected as copredictors, along with surgical status. Our findings suggest that for patients with high-grade glioma, time to progression after radiation therapy is influenced by both underlying biological aggressiveness (vascularity) and volume of aggressive tumor. In contrast, survival depends chiefly on the volume of aggressive tumor at the time of presentation.