Purpose: Concurrent chemoradiotherapy with 5-fluorouracil and cisplatin are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. S-l, an oral 5-fluorouracil derivative, is effective against esophageal cancer with mild toxicity and synergistic effects with radiation. This phase I trail was designed to determine the maximum tolerated dose and dose-limiting toxcity of S-l when given with thoracic radiotherapy in elderly patients.Methods: Patients who were histologically confirmed to have oesophageal cancer, were age 70 years or older, and had an Eastern Cooperative Oncology Group (ECOG) score of 0-2 were eligible for this study. Thoracic radiation therapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m2/day.Results: Between February 2010 and August 2011, 12 previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in 6 patients treated at the 60 and 70 mg/m2 dose levels. Dose-limiting toxicity was observed in 4 of 6 patients treated at the 80 mg/m2 dose level. Two patients developed grade 3 oesophagitis, 1 patient developed grade 3 oe-sophagitis and grade 3 pneumonitis, and 1 patient developed grade 3 thrombocytopaenia. Complete response (CR) and partial response (PR) was observed in 8 patients (66.7％) and 3 patients (25%), respectively.Conclusion: The recommended dose of S-l is 70mg/m2/day, and this is a feasible and well-tolerated regimen for the treatment of elderly patients with oesophageal cancer.