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Objectives: Proinflammatory cytokines triggered by surgery and postoperative pain are major causes of postoperative delirium (POD). This study investigated the effects of flurbiprofen axetil on POD when used for postoperative analgesia after major noncardiac surgery in elderly patients. Methods: Patients over 65 years old were randomly divided into two groups: the sufentanil group (S group), in which 150 μg of sufentanil was used in the patient‐controlled analgesia (PCA) pump for 3 days; the sufentanil combined with flurbiprofen axetil group (SF group), in which 150 μg of sufentanil was combined with 300 mg of flurbiprofen axetil in the PCA pump for 3 days. The Confusion Assessment Method scale was used for POD evaluation. The pain intensity, side effects, and risk factors (age, gender, surgical position, and category of surgery) for POD were evaluated. Results: Ultimately, 140 patients were included. The overall incidence of POD was not significantly different between the S and SF groups. The incidence of POD was significantly lower in the SF group than in the S group among patients over 70 years (5.1% vs. 20.7%, p = 0.045, odds ratio = 0.146, 95% confidence interval = 0.020–1.041). The incidence of POD was no difference in patients classified by the category of surgery, surgical position, or gender between groups. Sufentanil and flurbiprofen axetil in the PCA pump was completely used within 72 hr. The pain intensity, consumed sufentanil dosage of the PCA, and the side effects was not different between groups. Conclusions: Flurbiprofen axetil might reduce POD in patients over 70 years undergoing major noncardiac surgery. [ABSTRACT FROM AUTHOR]