With the dismal prognosis for malignant glioma patients, survival predictions become key elements in patient management. This study compares the value of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET and MRI for early outcome predictions in patients with recurrent malignant glioma on bevacizumab therapy. Methods: Thirty patients treated with bevacizumab combination therapy underwent18F-FLT PET immediately before and at 2 and 6 wk after the start of treatment. A metabolic treatment response was defined as a decrease of equal to or greater than 25% in tumor18F-FLT uptake (standardized uptake values) from baseline using receiver-operating-characteristic analysis. MRI treatment response was assessed at 6 wk according to the Response Assessment in Neurooncology criteria.18F-FLT responses at different times were compared with MRI response and correlated with progression-free survival and overall survival using Kaplan-Meier analysis. Metabolic response based on18F-FLT was further compared with other outcome predictors using Cox regression analysis. Results: Early and late changes in tumor18F-FLT uptake were more predictive of overall survival than MRI criteria (P < 0.001 and P = 0.01, respectively).18F-FLT uptake changes were also predictive of progression-free survival (P < 0.001). The median overall survival for responders was 3.3 times longer than for nonresponders based on18F-FLT PET criteria (12.5 vs. 3.8 mo, P < 0.001) but only 1.4 times longer using MRI assessment (12.9 vs. 9.0 mo, P = 0.05). On the basis of the 6-wk18F-FLT PET response, there were 16 responders (53%) and 14 nonresponders (47%), whereas MRI identified 9 responders (7 partial response, 2 complete response, 31%) and 20 nonresponders (13 stable disease, 7 progressive disease, 69%). In 7 of the 8 discrepant cases between MRI and PET,18F-FLT PET was able to demonstrate response earlier than MRI. Among various outcome predictors, multivariate analysis identified18F-FLT PET changes at 6 wk as the strongest independent survival predictor (P < 0.001; hazard ratio, 10.051). Conclusion: Changes in tumor18F-FLT uptake were highly predictive of progression-free and overall survival in patients with recurrent malignant glioma on bevacizumab therapy.18F-FLT PET seems to be more predictive than MRI for early treatment response. Copyright © 2012 by the Society of Nuclear Medicine, Inc.