Objectives: Although preoperative chemoradiation followed by surgery has been recognized as an efficient strategy for esophageal cancer treatments, several studies demonstrate survival benefits of postoperative chemoradiation for those undergoing upfront resection. The optimal sequence of surgery and chemoradiation remains unclear. Methods: Data of 1647 patients with clinical stage II/III esophageal squamous cell carcinoma (ESCC), including 1245 receiving preoperative chemoradiation followed by esophagectomy (pre-OP CRT group) and 402 receiving primary esophagectomy followed postoperative chemoradiation (post-OP CRT group), were obtained from a nationwide database. Propensity score matching identified 286 well-balanced pairs for outcome comparison. Results: In matched patients, the 3-year overall survival (OS) rates/median survival were not significantly different between the 2 groups (44.0% 3-year OS/26.0 months; 95% confidence interval [CI], 18.9-89 38.0 months) in the pre-OP CRT group, versus 37.9% 3-year OS/23.5 months (95% CI, 18.5-29.9 months) in the post-OP CRT group, P = .3152). The 3-year disease-free survival rates (DFS)/median survival after surgery were 38.7% 3-year DFS/16.7 months (95% CI, 11.9-29.6 months) in the pre-OP CRT group, compared with 30.2% 3-year DFS/10.4 months (95% CI, 7.61-.0 months) in the post-OP CRT group (P = .0674). In patients who had complete resection, the freedom from recurrence rate at 1 year after surgery was 74.8% and 67.6% in pre-OP CRT and post-OP CRT groups, respectively (P = .2696). In the multivariable analysis, treatment modality (pre-or post-OP CRT) was not a significant factor for OS (P = .258) or disease-free survival (P = .521). Conclusions: Similar outcome can be achieved with postoperative chemoradiotherapy compared with preoperative chemoradiotherapy in patients with locally advanced ESCC. There is little difference between these 2 strategies.