Multimodal therapy is increasingly utilized in the management of esophageal cancer. The optimum dose and fraction is unclear, and this retrospective analysis compared two radiation regimens in multimodality regimens where the chemotherapy arm and the type and magnitude of surgery was constant. Ninety-three consecutive patients with squamous cell carcinoma or adenocarcinoma of the esophagus were reviewed. Forty patients received the conventional unit regimen of 44 Gy in 22 daily fractions (2 Gy/fraction), and 40 patients received an increased dose per fraction (40 Gy in 15 daily fractions [2.67 Gy/fraction]). All patients received two courses of 5-fluorouracil and cisplatin and surgery was carried out within 8 weeks of completing therapy. The median overall survival in the group receiving the increased dose per fraction group was 25 months compared with 17 months in the conventional dose per fraction group (P=0.08). At 1, 3, and 5 years, 66%, 38%, and 38%, of patients in the increased dose per fraction group were alive, compared with 65%, 18%, and 15% in the conventional dose per fraction group (P=0.13), respectively. In the conventional dose per fraction group, two patients developed esophageal fistulae and one patient died postoperatively due to hemorrhage from an aorto-enteric fistula. There were no significant differences observed between treatment groups, but a trend toward improved efficacy appeared with the increased dose per fraction.