Background: Recovery from general anesthesia after endoscopic sinus surgery can abruptly become dangerous and having serious complications leading to lost intravenous cannulas, disconnected cables, self extubation, physical injury, increased pain and hemorrhage. This study aimed to evaluate the effects of adding ketamine to dexmedetomidine on smooth recovery from isoflurane anesthesia in adults undergoing endoscopic sinus surgery. Methods: A prospective double-blind randomized controlled study. Ten minutes before ending of surgery, 94 patients were randomly divided into two equal groups: Group (KD) (n = 47): received ketamine 0.5 mg/kg and dexmedetomidine 0.5ug/kg completed to 10 ml 0.9% normal saline and Group (C) (n = 47): received 10 ml 0.9% normal saline. Result: The extubation, recovery and discharge times were statistically significant prolonged in KD group (6.82 ± 0.76, 8.68 ± 0.81 and17.63 ± 4.8) min compared to C group (4.34 ± 0.61, 6.3 ± 0.72 and14.8 ± 2.7) min respectively. The median Ricker Sedation-Agitation scale (RSAS) score at the recovery time, at admission to PACU, at PACU and at discharge from PACU was statistically significant lower in KD group compared to C group (p < 0.0001). The mean Visual Analogue Scale (VAS) score on arrival to PACU, discharge from PACU, one hour, 2hs, 4hs, 8hs, 12hs and 24hs postoperative and pethidine requirements were statistically significant lower in KD group compared to C group (p < 0.0001). No statistically significant difference in side-effects between groups. Conclusion: Adding 0.5 mg ketamine to 0.5ug dexmedetomidine provides smooth recovery from isoflurane anesthesia in adults undergoing endoscopic sinus surgery.