OBJECTIVE: This study aims to identify blood biomarkers of postoperative delirium. BACKGROUND: Phosphorylated tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) are new Alzheimer disease biomarkers. Postoperative delirium is associated with Alzheimer disease. We assessed associations between Tau-PT217 or Tau-PT181 and postoperative delirium. METHODS: Of 491 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy, 139 participants were eligible and included in the analysis. Presence and severity of postoperative delirium were assessed in the patients. Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were determined by a newly established Nanoneedle technology. RESULTS: Of 139 participants (73±6 years old, 55% female), 18 (13%) developed postoperative delirium. Participants who developed postoperative delirium had higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than participants who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative Mini-Mental State score [odds ratio (OR) per unit change in the biomarker: 2.05, 95% confidence interval (CI):1.61-2.62, P <0.001 for Tau-PT217; and OR: 4.12; 95% CI: 2.55--6.67, P <0.001 for Tau-PT181]. The areas under the receiver operating curve for predicting delirium were 0.969 (Tau-PT217) and 0.885 (Tau-PT181). The preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were also associated with delirium severity [beta coefficient (β) per unit change in the biomarker: 0.14; 95% CI: 0.09-0.19, P <0.001 for Tau-PT217; and β: 0.41; 95% CI: 0.12-0.70, P =0.006 for Tau-PT181). CONCLUSIONS: Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were associated with postoperative delirium, with Tau-PT217 being a stronger indicator of postoperative delirium than Tau-PT181.