Objective: The serum albumin-globulin ratio (AGR) is associated with malignancy outcomes. However, among patients with rectal cancer (RC) who undergo neoadjuvant chemoradiotherapy (nCRT), the clinical and prognostic significance of the pretreatment AGR is unclear. Methods: We investigated whether the pre-nCRT AGR can help predict oncological outcomes in patients with RC receiving nCRT. We analyzed 114 patients with RC who received nCRT followed by total mesorectal excision at our institution. Results: A lower AGR in pre-nCRT serum was significantly correlated with shorter overall survival and disease-free survival in patients with nCRT-treated RC. In multivariate analysis, a high carcinoembryonic antigen (CEA) level and a low AGR in pre-nCRT serum were independent predictors of a poor prognosis in these patients. Furthermore, combining the AGR with CEA provided a more accurate indicator of poor prognosis and early recurrence in these patients. In particular, a low pre-nCRT AGR was a stronger indicator of a poor prognosis and early recurrence in patients without than with pathological lymph node metastasis. Combining the pre-nCRT AGR with CEA could more precisely stratify patients’ oncological outcome risks. Conclusion: Assessment of the pretreatment AGR with or without CEA can guide postoperative treatment in patients with RC who undergo nCRT.

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