This study was conducted to evaluate the efficacy and safety of Rituximab, Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab 375 mg/m2, i.v. on day 1; gemcitabine 1,000 mg/m2, i.v. on days 1 and 8, dexamethasone 40 mg i.v. on days 1-4, and cisplatin 25 mg/m2 i.v. on days 1-3, every 21 days. The primary end-points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. Eligible patients could then proceed to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up to six treatment cycles. From January 2005 to December 2010, 50 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory aggressive B-cell NHL, including diffuse large B-cell lymphoma (n=30) and follicular lymphoma grade 3b (n=20). The median follow-up time was 42 months (range, 12-70). After two cycles, the overall response rate was 72.0%, with a CR/CRu rate of 56%. The 2-year OS and PFS of all patients were 70.0 and 48.0%, respectively. Grade III-IV neutropenia and thrombocytopenia occurred in 34 and 40% of patients, respectively. Twenty-one patients (42%) proceeded to ASCT. Higher International Prognostic Index and refractory disease were independently associated with worse survival and progression-free survival. R-GDP chemotherapy in patients with refractory or relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for HDC/ASCT.