Background: The aim of this study was to investigate the diagnostic efficiency of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging in the evaluation of the recurrent contrast-enhancing regions at the location of treated gliomas. Patients and Methods: In 49 patients who had new contrast-enhancing lesions at the vicinity of previously resected and irradiated high-grade gliomas, single-voxel MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), lipid (Lip), and lactate (Lac) were analyzed in combination with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was allocated by means of follow-up or histopathology. Results: The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor group than in radiation injury group (p < 0.001). The ADC values and ADC ratios (quotient of ADC of contrast-enhancing lesion and matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p< 0.001). With MR spectroscopy, two variables (Cho/NAA and Cho/Cr ratios) were proved to differentiate recurrent glioma from radiation injury, and 81.5% of total patients were classified into correct groups. Using discriminant analysis for MR spectroscopy with diffusion-weighted imaging, three independent variables (Cho/NAA, Cho/Cr, and ADC ratio) could classify 91% of total patients into their correct groups. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square=4.15, p=0.042). Conclusion: MR spectroscopy combined with ADC ratio can enhance the ability to differentiate recurrent glioma from radiation injury.