Context: Critically ill patients requiring mechanical ventilation frequently need sedatives and analgesics to facilitate their care. Dexmedetomidine, a short-acting alpha-2-agonist, possesses anxiolytic, anesthetic, hypnotic, and analgesic properties. Aims: The objective of this study was to evaluate the efficacy and safety of dexmedetomidine in comparison to propofol in the management of sedation for post-operative intensive care unit (ICU) patients, as a sedative agent. Settings and Design: Teaching hospital, A phase III, prospective, open, randomized and comparative. Materials and Methods: Thirty patients who were ambulatory and who required the post-operative mechanical ventilation or post-operative sedation were enrolled, in which 15 patients received Dexmedetomidine and remaining 15 patients received propofol. All these patients were treated for the period of 8 to 24 h. Statistical Analysis Used: Data were analyzed using Student′s t-test and Chi-square test. The value of P < 0.05 was considered as statistically significant. Results: Demographic data were comparable. Pulse rate, respiratory rate and blood pressure were comparable. Depth of sedation and extubation time were similar. To maintain analgesia throughout the study period, patients receiving propofol infusions required significantly more analgesics than patients receiving Dexmedetomidine. Conclusions: Dexmedetomidine appears to be a safe and acceptable ICU sedative agent when both the clinician′s and patient′s perspectives are considered.