Breast cancer surgery is known to cause severe acute postoperative pain, which can persist for a long time. We administered nefopam preventively to patients undergoing lumpectomy with axillary lymph node dissection or sentinel lymph node biopsy, and evaluated its efficacy on acute and chronic postoperative pain.Enrolled patients were assigned to the nefopam (n = 41) or the control (n = 42) group. Before initiating the operation, 20 mg of nefopam was given to the patients of the nefopam group, and normal saline was used in the control group. Ketorolac was given at the end of surgery, and meloxicam was prescribed in the postoperative period to all patients in both groups. Pain was assessed using a numerical rating scale (NRS), and the rescue analgesic drug was given when the NRS was >5. Implementation of postoperative chemotherapy, radiotherapy (RT), or hormone therapy was evaluated.The NRS of postoperative pain was significantly lower in the nefopam than in the control group in the postanesthetic care unit (4.5 ± 2.2 vs 5.7 ± 1.5, respectively; P = 0.01), at postoperative 6 h (3.0 ± 1.6 vs 4.5 ± 1.3, respectively; P < 0.001), and at postoperative 24 h (3.1 ± 1.1 vs 3.8 ± 1.5, respectively; P = 0.01) with reduced use of rescue analgesic drugs. Significantly fewer patients suffered from chronic postoperative pain in the nefopam than in the control group at postoperative 3 months (36.6% vs 59.5%, P = 0.04). Considering only the cohort without postoperative adjuvant RT, the difference in the proportion of patients reporting chronic pain increased (23.5% in the nefopam group vs 61.5% in the control group, P = 0.04).Preventive nefopam was helpful in reducing the acute postoperative pain, with reduced use of rescue analgesic drugs, and it contributed to reduced occurrence of chronic pain at postoperative 3 months after breast cancer surgery.