Background: This study aimed to compare preoperative chemoradiotherapy (CRT) with postoperative CRT regarding survival, local control, disease control, sphincter preservation, toxicity and also prognostic factors for the treatment of locally advanced rectal cancer. Methods: Records of 140 patients with locally advanced rectal cancer who received preoperative or postoperative CRT were analyzed retrospectively. We compared the treatment groups (preoperative vs postoperative) according to baseline characteristics (demographic and rectal cancer disease characteristics), and also carried out the survival analyses. Results: From January 2010 to December 2019, 140 patients were included in the analysis, 65 received preoperative treatment and 75 postoperative treatment. There was no difference in survival, recurrence or distant metastasis rate in both treatment groups. The ratios of the failure to complete adjuvant chemotherapy (32% vs 4.6%) and acute grade 3–4 toxicity (32% vs 6.2%) were higher in the postoperative group (p < 0.001). In lower located tumors (≤5 cm from anal verge) the ratio of the sphincter preserving in the preoperative group was 60.7% (n = 17/28), and was 16.6% (n = 3/18) in the postoperative group (Yates χ2 = 5.829, p = 0.005). Conclusion: This study showed no difference in recurrence and survival rate. Preoperative CRT is the preferred treatment for patients with locally advanced rectal cancer, given that it is associated with a superior overall treatment compliance rate, reduced toxicity, and an increased rate of sphincter preservation in low-lying tumors, but not for overall survival.