Abstract: Background & Aims: Sedation and analgesia are important elements of endoscopic examinations; sedation for colonoscopy aims to relieve patient discomfort and anxiety, improve the outcome of the examination, diminish the patient’s memory of the event and achieve comfortable and technically successful endoscopic procedure. Methods: Our prospective study was carried out on 150 patients who were referred for colonoscopy; they were divided into two groups based on the pre-endoscopic sedation given for them: propofol fentanyl or propofol ketamine. Detailed histories, thorough physical examinations, and routine laboratory investigations were performed for all patients, along with monitoring of their vital signs and oxygen saturation levels (before, during and after colonoscopy), to assess safety, efficacy, recovery times, complications of the sedative drugs, comfort of the patients and endoscopists. Results: There was no statistically significant difference between the two groups in terms of age, sex and Body Mass Indexes (BMI). With respect to their Mean Arterial Blood Pressures (MAPs) and heart rates, there was high hemodynamic stability in the propofol ketamine group, and both the groups were efficacious, although the propofol fentanyl group had shorter recovery times than the propofol ketamine group (3±1.7 minutes and 4±2.8 minutes, respectively). However, nausea, vomiting and hypoxia were common in the propofol fentanyl group, while hallucinations were common in the propofol ketamine group. In propofol fentanyl group; there was a significant decrease in the heart rate more common in females (with age range 39-58 years) during and after colonoscopy [p value 0.01]. Conclusion: Sedation with propofol ketamine during colonoscopy was found to be safe and efficacious to achieve hemodynamic stability with fewer complications than propofol fentanyl.