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STUDY DESIGNS Retrospective Observational StudyObjectives: To compare the incidence of POD after propofol- and sevoflurane-based anesthesia in elderly patients undergoing spine surgery. METHODS In this study, the medical records of elderly patients ≥ 65 years of age who underwent spine surgery under total intravenous anesthesia with propofol or inhalational anesthesia with sevoflurane were reviewed. The primary outcome was the incidence of POD after propofol- and sevoflurane-based anesthesia. Secondary outcomes included postoperative 30-day complications, length of postoperative hospital stay, associations of patient characteristics, and surgery- and anesthesia-related data with the development of POD, and associations of anesthetics with clinical outcomes such as postoperative 30-day complications, and length of postoperative hospital stay. RESULTS Of the 281 patients, POD occurred in 29 patients (10.3%). POD occurred more frequently in the sevoflurane group than in the propofol group (15.7% vs. 5.0%, respectively; P=.003). The multivariable logistic regression analysis showed that sevoflurane-based anesthesia was associated with an increased risk of POD compared with propofol-based anesthesia (odds ratio [OR], 4.120; 95% confidence interval [CI], 1.549-10.954; P = .005), whereas anesthetics were not associated with postoperative 30-day complications and the length of postoperative hospital stay. Older age (OR, 1.242 CI, 1.130-1.366; P < .001) and higher mean pain score at postoperative day 1 (OR, 1.338 CI, 1.056-1.696; P = .016) were also associated with an increased risk of POD. CONCLUSIONS Propofol-based anesthesia was associated with a lower incidence of POD than sevoflurane-based anesthesia in elderly patients after spine surgery.