BACKGROUND:: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Gemcitabine, methylprednisolone, cisplatin +/− rituximab (GEM-P+/−R) is a salvage regimen with limited overlap in toxicity with first-line therapy and short duration of inpatient delivery. METHODS:: We assessed the efficacy and safety of GEM-P+/−R in a retrospective single-centre analysis including patients meeting criteria of ≥18 yr of age, histologically proven DLBCL, treated between 2001 and 2011 in second-line with gemcitabine 1000 mg/m day 1, 8 and 15, methylprednisolone 1000 mg day 1–5, cisplatin 100 mg/m day 15 (replaced with carboplatin AUC5 if contraindication/toxicity) +/− rituximab 375 mg/m day 1 and 15, every 28 d. RESULTS:: Forty-five patients aged 25–74 received a median of three cycles of GEM-P+/−R; 64% received rituximab. In 44 evaluable patients receiving GEM-P+/−R, overall response rate (ORR) was 48%; in 28 evaluable patients treated with rituximab + GEM-P (R-GEM-P), ORR was 61%. With median follow-up of 50.5 months (95% CI: 28.3–72.7), 3-yr overall survival (OS) from start of GEM-P+/−R was 31.4% (95% CI: 16.5–46.3); in patients treated with R-GEM-P, 3-yr OS was 49.1% (95% CI: 28.7–69.5). Predominant grade ≥ 3 toxicities were haematological; thrombocytopenia 69%, neutropenia 60% and febrile neutropenia 7%. CONCLUSION:: R-GEM-P is a deliverable regimen with useful activity in second-line treatment of DLBCL. Our data suggest that rituximab should be given concurrently.