Tumor status, as determined by positron emission tomography or gallium scanning (PET/G), may be an important predictor of outcome for patients with diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT). ASCT conditioning regimens that include rituximab may reduce the rate of relapse. We evaluated the influence of rituximab on overall and progression-free survival in patients with DLBCL based on PET/G status before ASCT. A retrospective review of all patients with chemosensitive DLBCL who underwent ASCT in the context of research protocols at our institution between 1995 and 2005 was performed. Our study included 174 patients. Disease status before ASCT, according to PET/G, was negative in 136 patients (78%), positive in 29 patients (17%), and unknown in nine patients (5%). PET/G status and rituximab use were the only factors predictive of progression-free survival in multivariate analyses: the hazard ratios for relapse were 2.9 for PET/G-positive versus -negative patients (P < 0.001) and 0.4 for rituximab versus no rituximab use (P = 0.001). We conclude that evidence of disease on PET/G scanning prior to transplantation is associated with an increased risk for relapse after ASCT. Transplantation regimens containing rituximab can reduce this risk, regardless of PET/G status.