Abstract: Objective To observe the effects of gabapentin and low-dose ketamine on the prevention of hyperalgesia induced by remifentanil anesthesia. Methods A total of 80 patients who underwent endoscopic hysterectomy under general anesthesia were randomly divided into four groups: a control group (Group C), a gabapentin group (Group G), a ketamine group (Group K), and a gabapentin + ketamine group (Group GK). The incidence of hyperalgesia of each group was observed 1 and 24 h after surgery. The scores of VAS were assessed 30 min (T1), 1 h (T2), 2 h (T3), 4 h (T4), 8 h (T5) and 24 h (T6) after surgery. The times of PICA usage and adverse reactions within 24 h after surgery were recorded. Results Compared with Group C, Group GK produced a remarkably lower incidence of hyperalgesia 1 h after surgery (P<0.05). The VAS scores and the times of PICA usage of Groups G, K and GK were significantly lower than that of Group C (P<0.05). Compared with Groups G and K, the VAS scores and the times of PICA usage were significantly decreased in Group GK (P<0.05). Groups G and GK reported lower incidences of nausea and vomiting within 24 h after surgery than Groups C and K (P<0.05). There was no significant difference among Groups C, G, K and GK in the incidence of other adverse reactions after surgery (P＞0.05). Conclusions The combined use of gabapentin and ketamine can effectively relieve post-operative hyperalgesia, reduce the dose of analgesics, and prevent postoperative nausea and vomiting.