Postoperative delirium is one of the most common postoperative complications in older patients. Its pathogenesis and biomarkers, however, remain largely undetermined. Majority of human microbiota is gut microbiota and gut microbiota has been shown to regulate brain function. Therefore, this study aimed to determine the association between gut microbiota and postoperative delirium in patients. Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium was assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota. Using principal component analyses along with a literature review to identify biologically plausible mechanisms, and three bacterials were studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0-76.0, 25%-75% percentile of quartile), 53% female], ten (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09-4.17, P = 0.026) was associated with postoperative delirium after adjusting for age and sex. The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33-1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27-1.24, P = 0.158) did not meet statistical significance. These findings suggest that postoperative gut microbiota (e.g., Parabacteroides distasonis ) may serve as biomarkers in the pathogenesis of postoperative delirium, pending confirmative studies.