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Among the different adjuvants, dexamethasone is one of the most accepted to prolong the effect of local anesthetics. This study aims to determine the superiority of perineural over systemic dexamethasone administration after a single-shot ankle block in metatarsal osteotomy.We performed a prospective, double-blind, randomized study. A total of 100 patients presenting for metatarsal osteotomy with an ankle block were randomized into 2 groups: 30 mL ropivacaine 0.375% + perineural dexamethasone 4 mg (1 mL) + 2.5 mL of systemic saline solution (PNDex group, n = 50) and 30 mL ropivacaine 0.375% + 1 mL of perineural saline solution + intravenous dexamethasone 10 mg (2.5 mL) (IVDex group, n = 50). The primary end point was the duration of analgesia defined as the time between the performance of the ankle block and the first administration of rescue analgesia with tramadol.Time period to first rescue analgesia with tramadol was similar in the IVDex group and the PNDex group. Data are expressed as mean (SD) or median (range). Duration of analgesia was 23.2 (9.5) hours in the IVDex group and 19 (8.2) hours in the PNDex group (P = 0.4). Consumption of tramadol during the first 48 hours was 0 mg (0–150 mg) in the IVDex group versus 0 mg (0–250 mg) in the PNDex group (P = 0.59). Four (8%) and 12 (24%) patients reported nausea or vomiting in the IVDex group and the PNDex group, respectively (P = 0.03).In front-foot surgery, perineural and systemic administrations of dexamethasone are equivalent for postoperative pain relief when used as an adjuvant to ropivacaine ankle block.This study was registered at ClinicalTrials.gov, identifier NCT02904538.