Background: Pregabalin is used for the treatment of neuropathic pain and has shown analgesic efficacy in post-operative pain. The aim of this randomized, double-blinded, placebocontrolled trial (Clinical Trials.gov ID NCT00938548) was to investigate the efficacy and safety of pregabalin for reducing post-operative pain in patients after mastectomy. Methods: Eighty-four women scheduled for elective mastectomy were randomly assigned to groups that received either pregabalin (75 mg) or placebo, 1 h before surgery and 12 h after the initial dose. Assessments of pain [verbal numerical rating scale (VNRS), at rest and with arm abduction] and side effects were performed at 1, 6, 24 and 48 h post-operatively. After discharge from the hospital, pain was assessed by telephone interview at postoperative 1 week and 1 month. Results: VNRS scores for pain at rest were lower in the pregabalin group (n 5 42) than the placebo group (n 5 42) at 1, 24 and 48 h post-operatively (Po0.05). VNRS scores for pain with arm abduction were lower in the pregabalin group (n 5 42) than the placebo group (n 5 42) at 1 and 24 h, and 1 week post-operatively (Po0.05). Incidences of side effects such as nausea and vomiting, headache, dizziness and blurred vision were similar in both groups. Conclusion: Perioperative administration of pregabalin for a single day (75 mg twice daily) was easy, safe and effective in reducing post-operative pain in patients undergoing mastectomy.