Objective To compare the efficacy between three-dimensional radiotherapy (3DRT) combined with chemotherapy and radiotherapy alone for patients with esophageal squamous cell carcinoma.Methods A retrospective analysis was performed for 1257 patients with esophageal squamous cell carcinoma who were admitted to our hospital from July 2003 to June 2012 and met the inclusion criteria;362 patients were treated with 3DRT combined with chemotherapy (chemoradiotherapy group) and 895 patients were treated with radiotherapy alone (radiotherapy group).The short-term outcome, overall survival (OS) rate, and causes of death were analyzed.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The response rate was 99.1%(346/349) in the chemoradiotherapy group and 99.0%(813/821) in the radiotherapy group (P=0.397).The 1-, 3-, and 5-year OS rates were 74.0%,42.0%,and 32.9% in the chemoradiotherapy group and 65.9%,33.0%,and 23.3% in the radiotherapy group (P=0.000), and were 75.6%,43.5%,and 33.2% in the concurrent chemoradiotherapy group and 65.9%,33.0%,and 23.3% in the radiotherapy group (P=0.000).There were no significant differences in 1-, 3-, and 5-year OS rates between the concurrent chemoradiotherapy group and the sequential chemoradiotherapy group (P=0.583).The sequential chemoradiotherapy group had an insignificant increase in 1-, 3-, and 5-year OS rates compared with the radiotherapy group (P=0.065).Tumor recurrence and local control failure were the main causes of death, followed by distant metastasis.The chemoradiotherapy group had a significantly lower proportion of patients who died of local control failure than the radiotherapy group (7.4% vs.14.7%, P=0.003).Conclusions For patients with esophageal squamous cell carcinoma, chemoradiotherapy leads to significantly improved overall survival compared with radiotherapy alone;compared with radiotherapy alone, sequential chemoradiotherapy results in an increasing trend in OS rates, while concurrent chemoradiotherapy results in significantly increased OS rates.Chemoradiotherapy can reduce the deaths due to local control failure compared with radiotherapy alone.