Background: The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). Methods: The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically. Results: A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LEES and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LEES or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups. Conclusions: The short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.