PURPOSE To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. METHODS AND MATERIALS The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. RESULTS There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. CONCLUSIONS The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.