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Background: This randomized, double-blind controlled trial was conducted to determine whether the association of sevoflurane for induction and isoflurane for anesthesia maintenance resulted in a lower incidence of postoperative agitation compared with sevoflurane as single agent., Methods: After Institute Ethics Committee's approval and parental written informed consent, 128 unpremedicated children (1-6 years), ASA I-II, scheduled for elective subumbilical surgery were enrolled. After induction with 8% sevoflurane, patients were randomly allocated to receive sevoflurane or isoflurane 1-1.5 MAC as maintenance agent. The primary endpoint of the study was the incidence of postoperative agitation defined as a screaming and crying child and/or a child that required physical restraint during emergence., Results: Eighteen children were excluded because they received sedatives, analgesia or anesthesia or because of ineffective regional analgesia before randomization. Fifty-four patients receiving sevoflurane and 56 receiving isoflurane completed the study. Twenty-eight children (95% CI 38-66%) in the sevoflurane group presented with postoperative agitation compared with 18 (95% CI 20-46%) patients receiving isoflurane (P = 0.028). Fifteen minutes after awakening, 11/54 children receiving sevoflurane were agitated compared with 4/56 receiving isoflurane (P = 0.03). Thereafter, there was a gradual reduction in the incidence of postoperative agitation over time., Conclusions: The association of sevoflurane for induction and isoflurane for maintenance produced significant less postoperative agitation in preschool children receiving regional anesthesia during subumbilical surgery compared with sevoflurane for induction and maintenance.