Background: The standard treatment of resectable esophageal cancer in Japan is neoadjuvant chemotherapy (NAC) followed by surgery, while definitive chemoradiotherapy (CRT) is considered as an alternative treatment. There are no randomized clinical trials comparing NAC and CRT in Japan. The aim of this study was to evaluate the efficacy of NAC or CRT in clinical practice. Methods: We retrospectively analyzed the clinical data of 43 patients (pts) with clinical stage IB/II/III thoracic esophageal squamous cell carcinoma (ESCC) who received NAC (n = 26) or CRT (n = 17) in Hokkaido University Hospital from January 2009 to December 2014. To compare NAC with CRT, Fisher’s exact test or Mann-Whitney U test was used in terms of pts’ characteristics, and Log-rank test was used in progression-free survival (PFS) and overall survival (OS). Results: Pts’ characteristics were as follows; Gender (male/female): 24/2 in NAC and 16/1 in CRT, median age (range): 65y (55-78) in NAC and 72y (57-80) in CRT, primary lesion (Ut/Mt/Lt): 4/12/10 in NAC and 2/9/6 in CRT, clinical stage IB-II/III: 11/15 in NAC and 9/8 in CRT. Four pts (15.4%) in NAC and seven pts (41.2%) in CRT had multiple primary cancer. All pts in NAC and 15 pts in CRT received 5-FU+cisplatin (CDDP), and two pts in CRT received 5-FU+nedaplatin. RT dose in CRT was 50.4Gy in 11 pts, 59.4Gy in five pts and 60Gy in one patient. Four out of 10 pts in NAC with local recurrence received salvage CRT, and three out of 10 pts in CRT with local recurrence received salvage surgery. Median PFS was 21.6 months in NAC and 8.7 months in CRT (HR 1.282, 95% confidence interval (CI) 0.871-1.887, p = 0.203), and median OS was 50.4 months in NAC and 48.6 months in CRT (HR 1.151, 95% CI 0.752-1.761, p = 0.516). 5-year OS rate was 49.7% in NAC and 48.3% in CRT. Conclusions: Definitive CRT showed comparable outcome to NAC followed by surgery in pts with resectable thoracic ESCC. Efficacy of NAC or CRT were not sufficient compared to clinical trials. Improvement in efficacy by development of optimal multimodality therapy was warranted.