Many studies have reported the prognostic value of pretreatment serum carcinoembryonic antigen (pre-CEA) levels on colorectal cancer outcomes. However, controversy remains concerning the significance of pre-CEA levels in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Our aim in this study was to investigate the prognostic role of the pre-CEA level in patients with locally advanced rectal cancer undergoing neoadjuvant CRT followed by total mesorectal excision (TME).A total of 419 patients with stages II and III rectal cancer treated with neoadjuvant CRT followed by TME with available pre-CEA data were included. The outcomes studied were 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Optimal pre-CEA cutoff values to predict DMFS were determined based on current smoking history.The median pre-CEA level of smokers was 3.8 ng/mL, and that of nonsmokers was 2.8 ng/mL (P < 0.01). Pre-CEA levels of 6.6 ng/mL for nonsmokers and 11.4 ng/mL for smokers were determined to best separate patients on the basis of time to distant metastasis by using log-rank statistics. The pre-CEA level was associated with DMFS (hazard ratio = 1.743, 95% confidence interval = 1.129-2.690, P = 0.01). The pre-CEA level was not associated with LRFS or DFS.The pre-CEA level appears to be a significant preoperative prognostic factor. Moreover, it is as valuable as any known pathologic factor. Future studies evaluating oncologic outcomes should take into consideration the pre-CEA level.