Objective To evaluate the effects of neoadjuvant long-course chemoradiotherapy (CRT), neoadjuvant short-course radiotherapy (SCRT), and total neoadjuvant treatment (TNT) on chemoradiotherapy related complications and perioperative safety in mid-low rectal cancer patients. Methods The clinical data of 63 rectal cancer patients who received neoadjuvant (chemo) radiotherapies and surgery treatment in West China Hospital from Jul. 2014 to Feb. 2016 were retrospectively analyzed. According to the neoadjuvant regimen, the patients were divided into CRT group (n=15), SCRT group (n=30), and TNT group (n=18), and then the effects of these 3 kinds of neoadjuvant regimen on chemoradiotherapy related complications and perioperative safety were compared. Results ① Chemoradiotherapy related complications: among all the included 63 patients, 29 patients (46.0%) occurred chemoradiotherapy related complications, including radiation enteritis in 9 patients and bone marrow suppression in 25 patients. There were significant differences in the overall incidence of chemoradiotherapy related complications, incidence of radiation enteritis and bone marrow suppression (P≤0.001). The overall incidence of chemoradiotherapy related complications and incidence of bone marrow suppression of SCRT group were lower. ② Perioperative safety: no significant differences were found in the incidence of surgical complications, incidence of specific surgical complication, operation duration, intraoperative blood loss, and postoperative flatus time (P<0.05), but there was significant difference in the postoperative hospital stay among 3 groups (P=0.033), the postoperative hospital stay of SCRT group was shorter. Conclusion CRT, SCRT, and TNT have similar effect on the safety in the mid-low rectal cancer patients, which suggests that SCRT is worthy of further research and promotion.