Context: Support for non-Hodgkin′s lymphoma (NHL) with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL) in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine) regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%]) received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%]) with GPD (gemcitabine, dexamethasone, cisplatine) protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively). Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24) and 19.7% (15.9-23.5), respectively, for the GPD regimen and 10.9% (8.2-13.7) and 11.1% (95% CI 8.5-13.7), respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000), event-free survival (2.03, 1.64-2.52; P