150 elderly patients (> 60 years) undergoing elective spinal surgery were randomized to receive either intravenous (IV; n=50), intranasal (IN; n=50), or intratracheal (IE; n=50) dexmedetomidine prior to the induction of anesthesia. The primary outcome of interest was the incidence of delirium after 3 postoperative days. Secondary outcomes of interest included incidence of sore throat, bradycardia, tachycardia, hypotension, hypertension, postoperative nausea and vomiting (PONV), dizziness, heart rate, and the Pittsburgh Sleep Quality Index (PSQI). The IV group had a significantly lower incidence of postoperative delirium when compared to the IN group after 3 days. The IE and IV groups were similar in the incidence of postoperative delirium. The IV group showed a significantly higher incidence of bradycardia compared to the IN and IE groups. Alternatively, the incidences of hypertension and PONV were significantly lower in the IV group compared to IN.