Background: To minimize patient discomfort, anxiety and pain and to improve patient cooperation throughout the procedure and ease the performance of the procedure by the endoscopists conscious sedation is required. The main objective of this study is to explore and compare the safety and efficacy of dexmedetomidine versus midazolam in providing sedation aimed at endoscopy. Materials & Methods: A randomized, prospective study was directed in Pushpagiri institute of medical sciences Thirunalla Totally 60 patients were enrolled in this study & they were separated in two groups: Group M: Inj.Fentanyl 1 mcg/kg + Inj.Midazolam 0.04 mcg/kg. Group D: Inj.Fentanyl 1 mcg/kg + Inj. Dexmedetomidine 1 mcg/kg. Participants of either sex, aged 18-60 years of age undergoing diagnostic and therapeutic Endoscopy, with American Society of Anaesthesiologist (ASA) Grade I and II. Results: The mean arterial pressure was significantly lower at time-points 2 and 3 compared with time-point 1 in participants of midazolam group (p < 0.05). SpO2 and RSS scores were significantly higher in the dexmedetomidine group as compared to midazolam group at time-points 2 and 3. Participants in the dexmedetomidine group rated their overall satisfaction with the procedure higher as compared to midazolam group (p < 0.05). A total of 6 patients (dexmedetomidine group n = 1; midazolam group n = 5) believed that they required either more or less sedation than they acknowledged. No patient reported feeling any severe pain during the process. The amnesic effect was corresponding in both groups, with no patient reporting any recall of intra-procedure events. There were no clinically significant complications in either group. Conclusion: Our results are suggestive of that dexmedetomidine has a good safety outline and is an effective sedative for use in endoscopy. We conclude that Dexemeditamedine has Good, Effective, Safety, Awake analgesia but satisfactory throughout procedure due to hypotension and bradycardia due to alpha 2 agonist action compared to midazolam group.