Background <p>The current study aimed to investigate which one or certain combinations of preoperative comorbidities were associated with higher risk of postoperative delirium.</p> Methods <p>This propensity-score-matched cohort study analyzed a retrospective dataset of elderly patients undergoing surgery at the First Medical Center of the Chinese PLA General Hospital from January 2014 to April 2019. Univariate risk factors were selected by logistic regression, and then the combinations of these univariate factors were compared.</p> Results <p>We identified 1034 older patients developed postoperative delirium (POD) within seven days after surgery, and 3102 patients without POD were matched by propensity score matching analysis at a ratio of 1:3 for those with POD. Eight preoperative comorbidities, including hypertension, diabetes, atrial fibrillation, cerebrovascular disease, Parkinson’s disease, epilepsy, depression, and chronic obstructive pulmonary disease (COPD) were more common in patients diagnosed with POD after surgery than those without POD. Patients with POD were more likely to concurrently suffer from the combinations of hypertension and cerebrovascular disease, or hypertension and COPD.</p> Conclusions <p>Several preoperative comorbidities are associated with a higher risk of POD in older surgical patient. Those suffering from combinations of preoperative comorbidities were more likely to develop POD, and hypertension plays a central role in these combinations.</p>