Introduction Pain which persists after thoracotomy is well recognized, and activation of the N‐methyl‐d‐aspartate (NMDA) receptor could be a contributing factor. This study sought to establish whether ketamine given peri‐operatively could reduce persistent post‐surgical pain. Trial design Double‐blind, randomized, placebo‐controlled trial comparing low‐dose intravenous ketamine and saline placebo. Methods Seventy patients undergoing thoracotomy were randomized to receive either intravenous ketamine (0.1 mg kg−1 hr−1) or saline placebo for 96 hr, starting 10 min prior to surgery. A bolus dose of 0.1 mg/kg of ketamine/placebo was given prior to starting the infusion. Post‐operative analgesia consisted of either an epidural infusion or patient‐controlled analgesia (PCA), +/− a paravertebral infusion of local anaesthetic. Pain scores and opioid consumption were collected at 24 and 48 hr after surgery. Patients completed numeric pain scores (NPS), modified Brief Pain Inventory (BPI), the short form Leeds Assessment of Neuropathic Symptoms and Signs (S‐Lanss) at baseline, 6 weeks, 3, 6 and 12 months after surgery. Results There were no significant differences in post‐operative pain, except the ketamine group reported less pain at rest 48 hr after surgery (p = 0.03). The ketamine group requested significantly less morphine via PCA in the first 24 hr (p = 0.03). There were no differences in pain measures or opioid consumption at 6 weeks, 3, 6 or 12 months. Patients in the ketamine group were more lightheaded (p = 0.02) and experienced more vivid dreams (p = 0.001). Conclusions Ketamine reduced opioid consumption compared to placebo after surgery, but we were unable to detect any differences in persistent post‐surgical pain between the groups. Significance This study adds to the growing body of evidence advocating the use of ketamine to reduce opioid consumption. No previous studies of peri‐operative ketamine have followed patients for a year after thoracotomy. This study found no reduction in persistent post‐surgical pain.