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Objectives The aim of this study was to assess the impact of neoadjuvant chemoradiation on the pathologic response and survival of patients with rectal cancer. Background Colorectal cancer is one of the most common human malignancies; there are a number of potential advantages for using neoadjuvant chemoradiation. They include the ability to deliver higher doses of chemotherapy with radiation, downstage the tumor, which has been noted in 60–80% of patients, and to achieve a pathologic complete response, which occurs in 15–30% of patients. The ability to ‘shrink’ the tumor facilitates surgical resection and performs a sphincter-preserving operation, radiating tissues with a greater oxygen supply, and decreases the likelihood of developing radiation enteritis, because the small bowel is less likely to enter the pelvis. Patients and methods This study included 80 patients with operable cancer rectum. A total of 40 randomized patients were treated with neoadjuvant chemoradiotherapy (CRT) followed by surgery, and the other 40 patients underwent surgery without neoadjuvant CRT. The pathological response to neoadjuvant CRT with regard to tumor necrosis, size, negative margins, number and size of lymph nodes with operative findings with regard to resectability and blood loss were assessed and then the follow-up of patients was carried out and compared with another group. Results We detected a statistically significant difference between both groups with regard to some pathological responses, including grade of tumor differentiation, number and positivity of lymph nodes, perioperative complication, and disease-free survival but no difference in overall survival. Conclusion Neoadjuvant chemoradiation could affect the disease-free survival of patients with rectal carcinoma.