Background: At present, the primary treatment of esophageal cancer is surgery-based comprehensive treatment, including adjuvant therapy such as chemotherapy and/or radiotherapy. However, the role of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) with pathologically node-negative (pN0) disease is controversial. This study aimed to evaluate the impact of postoperative adjuvant therapy on survival in patients with pN0 ESCC. Methods: Patients with ESCC who underwent R0 esophagectomy in the Department of Thoracic Surgery of Sichuan Cancer Hospital from January 2008 to December 2013 were enrolled. Patients were divided into two groups: a surgery alone (Group S) group or a surgery + adjuvant therapy (Group S + A) group. The primary outcomes were overall survival (OS) and disease-free survival (DFS), and every consecutive case was followed up until death or the last follow-up. Results: A total of 387 patients with ESCC patients who had pN0 were enrolled in the study. After propensity score matching (PSM), each group consisted of 150 patients. In the overall cohort, the 5-year OS (75.6% vs. 69.7%; P=0.004) and 5-year DFS (64.9% vs. 48.2%; P=0.003) rates were higher in Group S + A than in Group S. In the matched samples, the same outcomes were observed (5-year OS: 75.6% vs. 69.7%, P=0.026; 5-year DFS: 67.6% vs. 69.6%, P=0.036). Multivariate regression analysis indicated that postoperative chemotherapy was associated with longer OS [hazard ratio (HR): 0.622, 95% confidence interval (CI): 0.416-0.928; P=0.02] and DFS (HR: 0.571, 95% CI: 0.390-0.836; P=0.004); in contrast, T3 stage tumors (HR: 1.953, 95% CI: 1.238-3.082; P=0.004) and <15 lymph node dissections (HR: 1.81; 95% CI: 1.238-2.648; P = 0.002) were found to be independent risk factors for pN0 ESCC. Conclusions: Adjuvant therapy, especially chemotherapy, prolonged OS and DFS for patients with ESCC who had pN0 disease. Fewer lymph node dissections and T3 stage tumors were independent risk factors for OS and DFS.