Abstract Purpose Postoperative delirium (POD) is considered the most common postoperative neurological complication in elderly patients. The aim of this study was to evaluate the efficacy of the administration of ketofol versus dexme detomidine (DEX) for minimizing POD in elderly patients undergoing urgent exploration for intestinal obstruction. Methods This prospective double-blinded randomized clinical trial was conducted on 120 elderly patients undergo ing urgent exploration for intestinal obstruction. Patients were randomly allocated to one of the three groups: Group C (control group) patients received normal saline 0.9%, group D received dexmedetomidine, and group K received ketofol (ketamine: propofol was 1:4). The primary outcome was the incidence of POD. Secondary outcomes were incidence of emergence agitation, postoperative pain, consumption of rescue opioids, hemodynamics, and any side effects. Results The incidence of POD was statistically significantly lower in ketofol and DEX groups than in the control group at all postoperative time recordings. Additionally, VAS scores were statistically significantly decreased in the keto fol and DEX groups compared to the control group at all time recordings except at 48 and 72 h postoperatively, where the values of the three studied groups were comparable. The occurrence of emergence agitation and high dose opioid consumption postoperatively were found to be significant predictors for the occurrence of POD at 2 h and on the evening of the 1st postoperative day. Conclusion The administration of ketofol provides a promising alternative option that is as effective as DEX in reduc ing the incidence of POD in elderly patients undergoing urgent exploration for intestinal obstruction.