One of the most common complications after cardiac surgery with cardiopulmonary bypass (CBP) is delirium. The purpose of this study was to prospectively investigate the risk of developing postoperative delirium in a group of elderly patients using a multivariate assessment of preoperative and intraoperative risk factors. A total of 149 elderly patients were included. Thirty patients (20%) developed post-operative delirium. Preoperative procalcitonin (PCT) above the reference range (>0.05 ng/mL) was recorded more often in patients who postoperatively developed delirium than in the non-delirium group (50% vs. 27%, = 0.019). After surgery, PCT was significantly higher in the delirium than the non-delirium group: ICU admission after surgery: 0.08 ng/mL vs. 0.05 ng/mL = 0.011), and for consecutive days (day 1: 0.59 ng/mL vs. 0.25 ng/mL, = 0.003; day 2: 1.21 ng/mL vs. 0.36 ng/mL, = 0.006; day 3: 0.76 ng/mL vs. 0.34 ng/mL, = 0.001). Patients with delirium were older (74 vs. 69 years, = 0.038), more often had impaired daily functioning (47% vs. 28%, = 0.041), depressive symptoms (40% vs. 17%, = 0.005), and anemia (43% vs. 19%, = 0.006). In a multivariable logistic regression model, preoperative procalcitonin (odds ratio (OR) = 3.05), depressive symptoms (OR = 5.02), age (OR = 1.14), impaired daily functioning (OR = 0.76) along with CPB time (OR = 1.04) were significant predictors of postoperative delirium.