Objective To investigate the effects of intravenous high‑dose vitamin C (Vit C) on postoperative acute pain and early recovery in patients undergoing total laparoscopic hysterectomy and discuss the possible mechanism of inflammatory factors. Methods A total of 165 patients who were scheduled for laparoscopic hysterectomy were selected. According to the inclusion and exclusion criteria, 92 patients were enrolled and divided into two groups according to the random number table method: a test group (n=46) and a control group (n=46). The test group was intravenously infused with Vit C solution (20 mg·kg−1·h−1) followed by anesthesia induction. The control group received an equal volume of normal saline at the same rate. Patients in both groups underwent the same anesthesia procedures followed by patient‑controlled intravenous analgesia. The incidence of nonsurgical wound pain (NWP) and the resting and coughing Visual Analog Scale (VAS) scores 4, 8, 12, 24 h, and 48 h after surgery were recorded. The consumption of sufentanil within 48 h after operation and the adverse reactions were recorded. Preoperative and postoperative concentrations of serum interleu kin‑6 (IL‑6), interleukin‑10 (IL‑10) and 5‑hydroxytryptamine (5‑HT) were measured by enzyme‑linked immunosorbent assay (ELISA). The time of first out‑of‑bed activity, the time of first anal exhaust, the time of removing urine tube, and the length of hospitalization stay were also recorded. Results The test group presented remarkably decreased incidences of NWP 4, 8, 12 h and 24 h after surgery, compared with the control group (P<0.05), while there was no statistical difference between the two groups 24 h after surgery (P>0.05). Furthermore, no statistical difference was found in the resting and coughing VAS scores between the two groups (P>0.05). The consumption of sufentanil during the first 48 h in the test group was less than that in control group (P<0.05). There was no statistical difference in adverse reaction incidence between the two groups (P<0.05). After surgery, the concentrations of plasma IL‑6, IL‑10 and 5‑HT of the two groups were higher than those before surgery (P<0.05); the increases in the concentrations of IL‑6 and 5‑HT of the test group were less than those in the control group, while the increase in IL‑10 concentration of the test group was more than that in the control group (P<0.05). The test group showed significantly decreased time of first out‑of‑bed activity and the time of first anal exhaust, compared with the control group (P<0.05). There was no statistical difference in the time of first anal exhaust between the two groups (P<0.05). The test group presented remarkable decreases in the length of hospitalization stay than the control group (P>0.05). Conclusions Intravenous high‑dose Vit C can reduce the incidence of NWP after total laparoscopic hysterectomy, reduce postoperative analgesic consumption and promote early recovery. Inhibition of excessive inflammatory reactions and decrease of 5‑HT concentrations may be one of analgesic mechanism.