Abstract Background The CROSS trial established neoadjuvant chemoradiotherapy (CRT) as a cornerstone in treating esophageal cancer, making it the standard approach worldwide. However, in Japan, the JCOG1109 trial, a three-arm study, redefined the standard by showing the superiority of neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) over the conventional cisplatin and 5-fluorouracil (CF) regimen. Notably, it found no significant difference between neoadjuvant CRT with CF and CF. This trial adopted a 3-week cycle of 3 courses for the DCF regimen. Nonetheless, subsequent findings by Makino et al. suggested no difference in outcomes between 2-course and 3-course DCF regimens. This report presents the results of a 2-course neoadjuvant DCF regimen at our institution. Method This study included esophageal cancer patients who underwent esophagectomy after a 2-course NAC-DCF regimen at Okayama University Hospital from January 2014 to December 2019. Eligible participants were 20 to 80 years old, with a performance status of 0–1, histologically confirmed esophageal squamous cell carcinoma (ESCC), and adequate organ function. The stages ranged from cT1-4a N0-3 M0. We evaluated recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) using the Kaplan-Meier method and explored histopathological factors associated with RFS through COX regression analysis. Results Out of 209 cases, 63 were eligible. The median follow-up was 71 months, with 17 instances of recurrence observed, categorized as lymphatic (6 cases), hematinic (3 cases), local (2 cases), dissemination (2 cases), and multiple (4 cases). The 5-year RFS was 64.5%, and the 5-year OS was 65.8%. Univariate analysis identified pathological T, N, Stage, and chemotherapy response grade as significant factors related to RFS, with multivariate analysis highlighting pathological N as an independent factor. Kaplan-Meier analysis demonstrated significant survival differences across N stages, particularly between N1 and N2. Conclusion Our findings from the 2-course neoadjuvant DCF regimen highlight pathological N stage as a crucial independent predictor of recurrence in ESCC patients treated with NAC-DCF. Specifically, patients above N2 exhibited notably poorer prognoses, underscoring the need for adjuvant treatment strategies.