The aim of the study was to evaluate the feasibility and efficacy of treatment with oxaliplatin, 5-fluorouracil and leucovorin concomitant with radiation therapy in locally advanced oesophageal cancer. Fifty-eight patients with previously untreated, histologically proven oesophageal cancer were enrolled. Downstaged patients underwent either surgery or received brachytherapy. We report the results obtained in the first 54 patients. The median age was 58 years. The diagnosis was squamous cell carcinoma/adenocarcinoma/poorly differentiated: 45/8/1; clinical stage: T3N1M0 38 (70%), T4 10 (19%), M1a 6 (11%). Thirty-nine patients (72%) received the planned 8 weeks of chemotherapy and 45 completed the entire course of scheduled radiotherapy. Four (7%) toxic deaths were recorded, 2 more patients died prematurely from massive oesophageal bleeding and 1 from progression of disease. We recorded 8 (15%) complete responses and 24 (44%) partial responses. Resection was complete (R0) in 24 (80% of resected patients, 44% of treated patients). A complete pathological response was documented in 6 patients (11% of those treated). Postoperative complications were recorded in 8 (25%) patients, with 2 (6.2%) deaths. RO resection was accomplished in 44% of patients. Toxicity was moderate, but postoperative mortality was not negligible. Survival data are awaited before a phase III comparison with cisplatin-containing chemo-radiotherapy may be considered.