Background:Rebound pain after single shot nerve block challenges the real benefit of this technique. We aimed to investigate whether perineural dexamethasone addition decreased the incidence of rebound pain after a single shot nerve block.Methods:We randomly allocated 132 patients scheduled for open reduction, and internal fixation of upper extremity closed fracture under single-shot peripheral nerve block and sedation into two groups. Patients in the dexamethasone group receiving nerve block with 0.375% ropivacaine and 8 mg dexamethasone while those in the control group received ropivacaine only. Sixty-three cases in the dexamethasone group and 60 cases in the control group were analyzed for the incidence of rebound pain in 48 h after the block administration. The primary outcome was the incidence of rebound pain in 48 h after the block administration. Secondary outcomes included the self-reported highest NRS score, pain intensity at 8h, 12h, 24h, 48h after the block, sufentanil consumption, sleep quality on the night of surgery, patient’s satisfaction to the pain therapy, blood glucose at 6h after the block, pain and paresthesia at 30 days after surgery.Results: The incidence of rebound pain was significantly lower in the dexamethasone group (7[11.1%] of 63 patients) than that in the control group (28[48.8%] of 60 patients; Relative risk (RR) is 0.238, 95% CI 0.113-0.504,p=0.001). Dexamethasone decreased the opioid consumption in 24 h after the surgery (p<0.001), improved the sleep quality score on the night of surgery(p=0.01) and satisfaction to the pain therapy(p=0.001). Multivariate logistic regression analysis showed that only group allocation was significantly associated with the occurrence of rebound pain[OR=0.131,95%CI (0.047-0.364)].Patients in the dexamethasone group reported later onset (19.7±6.6 h vs 14.7±4.8 h since block administration, mean±SD, p<0.001) lower peak NRS score [5 (3,6) vs 8 (5,9) , median(IQR), p<0.001] compared with those in the control group.Conclusions: Perineural administration of 8mg dexamethasone reduces rebound pain after a single-shot nerve block in patients receiving ORIF of upper limb fracture.Trial registration: This study was registered in Chinese Clinical Trial Registry (ChiCTR-IPR-17011365). The study was registered on May 11th , 2017. Retrospectively registered.