Introduction: There is a lack of information on the role of neoadjuvant chemotherapy in upper rectal cancer. The aim of our research was to investigate the role of neoadjuvant chemotherapy in upper rectal cancer treatment.Materials and methods: We conducted a retrospective cohort multicenter study to analyze the medical records of patients with upper rectal cancer from 2007 to 2020 obtained from the archive of Research Institute FSBI «N. N. Blokhin Cancer Research Center» of the Ministry of Health of Russia, A. N. Ryzhikh National Medical Research Centre for Coloproctology, Stavropol regional Clinical oncological Dispensary and Kaliningrad oncological Center. All patients were divided into 2 groups: group 1 included patients who underwent neoadjuvant chemotherapy with CAPOX as the first treatment step, and group 2 included patients who underwent upfront surgery. Primary endpoint was 3‑year disease-free survival (DFS) rate. We also estimated the pathological complete response (pCR) rate, treatment toxicity, postoperative morbidity rate (Clavien – Dindo), degree of tumor regression, local recurrence rate, distant metastases rate, 3‑year overall survival (OS) and the neoadjuvant chemotherapy completion rate.Results: 118 patients were included in the neoadjuvant chemotherapy group and 103 patients — in the surgery group. Study groups were well balanced and comparable for gender, the ASA status and the tumor differentiation grade. More patients in the neoadjuvant chemotherapy group had clinically positive lymph nodes (p = 0.002). Median follow-up period was 36 months. There were no significant differences in 3‑year OS and DFS. The local recurrence rate was 3.9 % in the surgery group versus 0 % in the neoadjuvant chemotherapy group (p = 0.046). There were no significant differences between study groups in the distant metastases rate (p = 0.293). Sixteen (13.6 %) patients had a pCR after neoadjuvant chemotherapy. The neoadjuvant chemotherapy completion rate was 91.5 %. The hematological toxicity grade 3–4 was observed in 3.3 % (4 patients), the non-hematological toxicity grade 3–4 in 3.3 % (4 patients).Conclusion: NACT has an acceptable toxicity profile, does not impede oncological treatment results, and can be used in a selected group of patients for early systemic control.