The prognostic accuracy of interim (18)F-fluoro-2-dexoy-D-glucose positron emission tomography/computerized tomography (PET/CT) using three different methods of response assessments during rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy was investigated in 186 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The response of interim PET/CT was assessed based on a combined evaluation of the Deauville five-point scale (5-PS), the rates of reduction in the maximal standardized uptake value (ΔSUVmax), and the rates of reduction in the metabolic tumor volume (ΔMTV2.5). Positivity on the 5-PS, the optimal cutoff of ΔSUVmax, or the optimal cutoff of ΔMTV2.5 could each predict disease progression. Over a median follow-up of 22.8 months, the assessment of responses based on the 5-PS, ΔSUVmax, and ΔMTV2.5 had prognostic value for progression-free survival. When patients were allocated a score of 0 to 3 depending on the presence of an inadequate response by visual, ΔSUVmax, or ΔMTV2.5, the outcomes of patients with a score of 0 were significantly superior to those with a score of 1, 2, or 3. The interim PET/CT response based on visual, SUV-based, and MTV-based assessment had significant negative predictive value for disease progression and a high potential for predicting outcomes of patients with DLBCL.