Objective To investigate the effectiveness of combined Pregabalin and Celecoxib for neuropathic pain after percutaneous endoscopic lumbar discectomy. Methods Between January and June 2014, 178 patients with lumbar disc herniation underwent percutaneous endoscopic interlaminar discectomy (PEID). Ninety patients who met the inclusion criteria were recruited in this study. Every case in group A was recruited to match its counterpart in group B and group C according to gender, disease duration, herniated level, smoking history, preoperative Leeds assessment of neuropathic symptoms and signs (LANSS), and Oswestry disability index (ODI). Nine patients were excluded due to incomplete study or loss of follow-up. In each group, 27 cases were included in the final analysis. There was no significant difference in gender, age, height, body mass index, herniated level, disease duration, smoking history, preoperative LANSS, ODI, and visual analogue scale (VAS) between groups (P>0.05). All patients of 3 groups received oral administration of Celecoxib from preoperative 3rd day to postoperative 14th day. Pregabalin was taken orally from preoperative 3rd day to postoperative 14th day in group A, and from postoperative 1st to 14th day in group B. Adverse drug reactions were observed during medication. The LANSS score and VAS score in rest state and active state were conducted before operation and at 1 day, 1 month, and 3 months after operation. ODI was conducted before operation and at 1, 3 months after operation. The number of neuropathic pain cases was recorded, and the effectiveness was evaluated by modified Macnab criteria at 3 months after operation. Results During period of increasing Pregabalin dose, 1 patient of group A suffered severe dizziness, and 1 patient of group B suffered sleepiness, who were eliminated from this research. Another 2 cases (1 case of group A and 1 case of group C) suffered dry mouth, and 1 case of group B suffered muscle weakness. At 1 day after operation, the LANSS score and VAS in rest state and active state of group A were significantly lower than those of groups B and C (P<0.05). At 1 month after operation, the LANSS score, ODI, and VAS in rest state and active state of group A and group B were significantly lower than those of group C (P<0.05). At 3 months after operation, the LANSS score, ODI, and VAS in active state of group A and group B were significantly lower than those of group C (P<0.05). There was no significant difference in the above indicators at the other time points between groups (P>0.05). Neuropathic pain occurred at 3 months after operation in 1 case (3.7%) of group A and 6 cases (22.2%) of group C, showing significant differences in incidence of neuropathy pain between groups A, B and group C (P<0.05), but no significant difference was found between group A and group B (P>0.05). The excellent and good rate of modified Macnab criteria was 92.6% in group A, was 88.9% in group B, and was 85.2% in group C at 3 months after operation, showing no significant difference between groups (P>0.05). Conclusion Combined use of Pregabalin and Celecoxib during perioperative period can reduce postoperative pain and incidence of postoperative neuropathic pain. Preoperative oral Pregabalin can reduce the incidence of acute postoperative neuropathic pain.