Interim 18F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma(DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis(PET/CT0), after 2 and 4 cycles of chemotherapy(PET/CT2 and PET/CT4, respectively), and at the end of treatment(F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate(75.8% vs. 38.2%) and 3-year overall survival rate(93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy(15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive. Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (I-PET / CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET / CT was performed at the time of diagnosis (PET / CT0), after 2 and 4 cycles of chemotherapy (PET / CT2 and PET / CT4, respectively), and at the end of treatment Lymphoma, 110 patients had negative PET / CT2 scans, and 87 had positive PET / CT2 scans. The PET / CT2-negative patients had significantly higher 3-year progression-free survival rates (75.8% vs. 38.2% Overall survival rate (93.5% vs. 55.6%) than PET / CT2-positive patients. All PET / CT2-negative patients rema ined negative at PET / CT4, but 3 were positive at F-PET / CT. Among the 87 PET / CT2-positive patients, 57 remained positive at F-PET / CT, and 32 progressed during chemotherapy 17 at F-PET / CT). Comparing PET / CT4 with PET / CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET / CT with PET / CT0, . In conclusion, our results indicate that I-PET / CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET / CT in the detection of relapse in PET / CT2-negative patients , but repeat PET / CT is required if the PET / CT2 findings are positive.