The development of a more effective and less toxic salvage regimen remains a major challenge in elderly patients with relapsed and/or refractory peripheral T-cell lymphoma (PTCL). From April 2004 to May 2010, we used a new salvage regimen combining gemcitabine, oxaliplatin and dexamethasone (GemOD) in 24 elderly patients with relapsed (n = 11) or refractory (n = 13) PTCL unsuitable for high dose therapy. GemOD consisted of gemcitabine (1000 mg/m(2) on day 1), oxaliplatin (100 mg/m(2) on day 1) and dexamethasone (20 mg/day from day 1 to day 4), which was given every 3 weeks. Patients were scheduled to receive up to six courses of GemOD therapy unless there was evidence of progressive disease. The median number of GemOD courses delivered was four (range 3-6). After three courses of GemOD, the overall response rate (ORR) was 38%, with two complete responses (CRs) and seven partial responses (PRs). Among 11 patients who received three additional planned courses of therapy, there were three CRs and three PRs, for an ORR of 25% after complete treatment as per the study protocol. With a median follow-up of 18 months, the median overall survival (OS) and event-free survival (EFS) reached 14 and 10 months, respectively. Hematologic and non-hematologic toxicities were moderate in all patients. We conclude that the GemOD regimen can be administered safely and effectively in elderly patients with relapsed and refractory PTCL who are ineligible for high dose chemotherapy with stem cell transplant.