Simple Summary This study investigated the effectiveness of proton beam therapy (PBT) for esophageal squamous cell carcinoma (ESCC). This research found that PBT showed promising results in terms of favorable overall survival rates and reducing toxicities in ESCC patients. The 3 year overall survival rates for patients with stages I, II, and III of ESCC were 81.0%, 62.9%, and 51.3%, with corresponding progression-free survival rates of 70.6%, 71.8%, and 39.8%. Notably, salvage procedures were successful at treating isolated local and regional progression, and severe lymphopenia cases were absent. This study supports the conclusion that PBT is an effective treatment option for ESCC patients in terms of both the survival outcomes and toxicity management.Abstract Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC). The 3 year overall survival (OS) and progression-free survival (PFS) rates were calculated based on stage grouping. The patterns of failure, salvage treatment outcomes, and toxicity profiles were analyzed. The median follow-up was 35.1 months, and 132 patients were analyzed. The 3 year OS and PFS rates for the stages I, II, and III disease cases were 81.0%, 62.9%, and 51.3%; and 70.6%, 71.8%, and 39.8%, respectively. Nineteen patients presented isolated local progression, ten patients underwent appropriate salvage procedures, and nine were successfully salvaged. One patient with isolated regional progression was also salvaged. No cases of grade >= 4 lymphopenia were observed. One patient had grade 4 pericardial effusion and esophageal fistula. For the patients with ESCC, PBT is an effective treatment in terms of the survival outcomes and toxicities.