Background: Preoperative chemoradiation therapy (CRT) and total mesorectal excision have been the standard care of the patients with locally advanced rectal cancer. Response to the preop CRT varied from patient to patient, approximately 10-15% of the patients achieved complete response, on the contrary, nearly 40% of the patients still showed ypT4 disease. The aim of this study is to assess the prognostic value of NLR and suggest the optimal cut-off value to predict tumor response to the preoperative chemoradiation therapy in the patients with locally advanced rectal cancer. Methods: We analyzed the medical records of 1134 patients who diagnosed with locally advanced rectal cancer and treated with preop CRT followed by radical surgery at St. Vincent hospital, Seoul St. Mary’s hospital, Chonnam National University Hwasun Hospital, Gyeongsang National University Hospital and Dongsan Medical Center from 1998 to 2015. All patients had histologically confirmed rectal adenocarcinoma within 10 cm from anal verge. All patients received preoperative CRT to the pelvis followed by TME. Complete blood count was performed at initial workup before treatment and NLR was calculated with differential count. Results: An optimal cut-off value of the NLR was revealed as 1.98. The NLR showed average value for predicting death (AUC 0.516, p < 0.001). According to the cut-off value, patients were divided into two groups; high NLR (NLR≥2.0, n = 530) and low NLR (NLR < 2.0, n = 604). The patients with low NLR achieved pathologic complete response more frequently. 105 patients of total 604 patients (17.4%) with low NLR showed no remnant tumor cells, compared to 63 patients of the 530 patients (11.9%) with high NLR did (p = 0.012). The proportion of the patients who were downstaged to T1-2N0 was evaluated. In the low NLR group, 258 patients (42.7%) were downstaged, while 199 patients (37.5%) in the high NLR group were, which showed a tendency but did not reach statistical significance (p = 0.087). Conclusions: In this large-scale multi-center analysis, NLR was once again identified as a predictor of treatment response of preop CRT in patients with locally advanced rectal cancer.