Background: Upper gastrointestinal (GI) endoscopy can cause pain and anxiety to the patients which in turn lead to hemodynamic instability and impairment in the patient tolerance. Consequently, adequate sedation and analgesia are required in such procedure to maintain the optimal conditions for patient's relief and recovery. Objective: This work aimed to determine whether the use of ketofol instead of propofol resulted in fewer adverse respiratory events requiring physician intervention when used for procedural sedation and analgesia. Patients and Methods:  After approval of the Medical Ethical Committee at Al-Azhar University Hospitals, and after patient written consents, 60 patients of American Society of Anesthesiologists (ASA) physical status I or II, scheduled for elective upper GI endoscopy under sedation  were enrolled in this randomized, controlled, prospective, double-blind, clinical trial study.  Patients were randomly assigned into two equal groups: Group (I)  received 0.5 mg /kg propofol i.v.  Within a period of 30-40 seconds. Group (II)  received 50mg ketamine plus 0.5 mg/kg propofol in 10 ml normal saline within a period of 30-40 seconds. Results: The dose of propofol was equal in both groups. Hypoventilation was significantly lower in the group (ІІ), compared to the group (І).      No significant difference was reported between both groups regarding hypoxia, heart rate, adverse effects, and systolic blood pressure, recorded after the procedure and 25-minute after the onset of procedure. Systolic blood pressure was significantly higher in the group (ІІ), compared to the group (І), throughout the 20 minutes following propofol induction. Conclusion: Combination of propofol and ketamine used for procedural sedation and analgesia in upper GI endoscopy had higher safety than the propofol alone. Respiratory and hemodynamic stability were more noted in the ketofol group than the propofol-only group.