ObjectiveTo evaluate the safety, functional protection, and clinical efficacy of three-dimensional (3D) complete laparoscopic radical rectal cancer resection using natural orifice specimen extraction surgery (NOSES). MethodsAccording to the inclusion and exclusion criteria, the patients who received laparoscopic radical rectal cancer surgery in the Second Affiliated Hospital of Chongqing Medical University from January 2019 to December 2020 were retrospectively collected. The patients underwent 3D complete laparoscopic radical rectal cancer resection using NOSES were allocated to the observation group, while traditional laparoscopic assisted radical rectal cancer resection were allocated to the control group. The indexes of safety, functional protection, and clinical efficacy were compared between the two groups. ResultsA total of 80 patients were included in this study, including 40 patients in the observation group and 40 patients in the control group. There were no statistical differences in the baseline data between the two groups (P>0.05). There were no statistical differences between the two groups in the total operative time, intraoperative bleeding, number of lymph node dissection, positive rates of intraperitoneal tumor cells and bacterial culture, and tumor recurrence and metastasis rate (P>0.05). Compared with the control group, the first getting out of bed time, exhausting and defecating time after operation were earlier, meanwhile the postoperative pain score, use of analgesics, and the occurrence of severe low anterior resection syndrome were better in the observation group (P<0.05). The incidence of postoperative overall complications in the observation group was lower than that in the control group (P<0.01). The postoperative hospital stay was shorter and the hospitalization costs were less in the observation group as compared with the control group (P<0.05). ConclusionFrom results of this study, 3D complete laparoscopic radical rectal cancer resection using NOSES is safe and feasible, its functional protection and clinical efficacy are better than those of traditional laparoscopic assisted radical rectal cancer resection.