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Perineural dexamethasone has gained popularity in regional anesthesia to prolong analgesia duration. However, uncertainty remains regarding the optimal perineural dose. Clarification of this characteristic is of significant importance as the administration of dexamethasone may lead to dose-dependent complications. The objective of this meta-analysis was to define the optimal perineural dexamethasone dose to prolong analgesia after brachial plexus blockade for adult patients undergoing upper limb surgery.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and searched databases including MEDLINE, PubMed, and EMBASE until January 2017, without language restriction. Only trials comparing perineural dexamethasone and local anesthetics with local anesthetics alone for brachial plexus blocks were included in the present meta-analysis. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the methodological quality of each trial and meta-analyses were performed following a random effects model. The primary outcome was duration of analgesia for each type of local anesthetic (short-/intermediate-acting and long-acting local anesthetics). A meta-regression followed by a subgroup analysis were performed to assess the impact of different perineural dexamethasone doses on duration of analgesia; for the latter analysis, trials were grouped in low (1–4 mg) and moderate (5–10 mg) dexamethasone doses. Secondary outcomes included the rate of neurologic complication and resting pain scores and morphine consumption within the first 24 hours.Thirty-three controlled trials, including 2138 patients, were identified. The meta-regression revealed a ceiling effect with a perineural dexamethasone dose of 4 mg when combined with short-/intermediate-acting (8 trials; 366 participants) or long-acting local anesthetics (23 trials; 1869 participants). This finding was confirmed by subgroup analyses comparing low and moderate dexamethasone doses. With short-/intermediate-acting local anesthetics, the mean difference (95% confidence interval) of analgesia duration with low and moderate doses was 277 (234–322) minutes and 229 (161–297) minutes, respectively. With long-acting local anesthetics, the mean differences with low and moderate doses were 505 (342–669) minutes and 509 (443–575) minutes. Perineural dexamethasone did not increase the rate of neurologic complications (risk ratio [95% confidence interval], 1.40 [0.54–3.63]). The Grades of Recommendation, Assessment, Development, and Evaluation quality of evidence for the primary and secondary outcomes were very low, due mainly to limitations, inconsistency, indirectness, and publication bias.There is currently very low quality evidence that 4 mg of perineural dexamethasone represents a ceiling dose that prolongs analgesia duration by a mean period of 6 and 8 hours when combined with short-/intermediate- or long-acting local anesthetics, respectively. Additional data are needed to explore the threshold for this effect, particularly with doses below 4 mg. The risk of neurologic complications is probably not increased (very low evidence).