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We conducted a prospective multicenter trial to compare the usefulness of 11C‐methionine (MET) and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11C‐MET and 18F‐FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty‐one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11C‐MET or 18F‐FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow‐up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11C‐MET PET and 18F‐FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85‐0.99) and 0.48 (16/33, 95% CI: 0.33‐0.65), respectively, and the difference was statistically significant (P <.0001). The diagnostic accuracy of 11C‐MET PET was significantly better than that of 18F‐FDG PET (87.5% vs. 69.6%, P =.033). No examination‐related adverse events were observed. The results of the study demonstrated that 11C‐MET PET was superior to 18F‐FDG PET for discriminating between tumor recurrence and radiation‐induced necrosis. [ABSTRACT FROM AUTHOR]