Background and AimsPrevious studies have focused on the role of perioperative nicotine replacement therapy (NRT) in improving the success rate of long-term smoking cessation in tobacco smokers. This study aimed to measure the effectiveness of high-dose NRT in alleviating postoperative pain for male abstinent smokers receiving abdominal surgery. DesignThis was a parallel-group, randomized, double-blind and controlled pilot trial. Setting and participantsIn total, 101 male smoking-abstinent patients from the Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from 8 October 2018 to 10 December 2021. InterventionsPatients started smoking cessation on admission to the hospital ward. Patients received 24-hour transdermal nicotine patches (n = 50) or placebo (n = 51) every day from admission until 48 hours after surgery. MeasurementsThe primary outcomes were pre-surgery pain thresholds and total consumption of analgesics within the first 48 hours after surgery. Secondary outcomes included postoperative pain and sedation scores, nausea, vomiting and fever frequency within the treatment period. FindingsBoth pre-surgery electrical and mechanical pain thresholds in the NRT group were higher than those in the placebo group (P = 0.004 and P = 0.020, respectively). The 48-hour postoperative analgesic consumption was significantly lower for smoking-abstinent patients receiving NRT than those receiving placebo (standardized morphine equivalent requirement, median [interquartile range], 1.80 [1.47, 2.32] mg/kg vs 2.22 [1.62, 2.82] mg/kg, P = 0.011). Postoperative pain intensity was significantly lower in the NRT group than that in the placebo group at 1st hour and 24th hour post-surgery (P < 0.001 and P = 0.012, respectively). The incidence of treatment-related adverse events was not significantly different between groups. ConclusionsPerioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.