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Forty-two patients with high-grade gliomas were enrolled in this study. The final diagnosis was determined by histopathologic analysis or clinical follow-up. PWI and PET parameters were recorded and compared between patients with recurrence and those with radiation injury using Student t tests. Receiver operating characteristic and logistic regression analyses were used to determine the diagnostic performance of each parameter. The final diagnosis was recurrence in 33 patients and radiation injury in 9. PET/CT showed a patient-based sensitivity and specificity of 0.909 and 0.556, respectively, while PWI showed values of 0.667 and 0.778, respectively. The maximum standardized uptake value, mean standardized uptake value, tumor-to-background maximum standardized uptake value, and mean relative CBV were significantly higher for patients with recurrence than for patients with radiation injury. All these parameters showed a significant discriminative power in receiver operating characteristic analysis. Both ¹¹C-methionine PET/CT and PWI are equally accurate in the differentiation of recurrence from radiation injury in patients with high-grade gliomas, and a combination of the 2 modalities could result in increased diagnostic accuracy.