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Introduction: Prolonged mechanical ventilation increases the risk of ventilator-associated pneumonia and delirium which can lead to an extended intensive care unit (ICU) duration. The Society of Thoracic Surgeons (STS) defines early extubation within 6 hours of cardiac surgery as a quality marker. Previous studies have demonstrated a shorter time to extubation in a dexmedetomidine-based sedation strategy compared to a propofol-based sedation strategy. This study compared the effects of propofol and dexmedetomidine as primary sedative agents in the time to extubation in adult cardiac surgery patients who underwent open-heart surgery. Methods: This retrospective cohort study conducted at the area’s largest center for comprehensive heart emergency care included adult patients who underwent elective or urgent open-heart surgery from January 2024 - September 2024. Patients were divided into two groups based on primary sedative agent received post open-heart surgery. The primary outcome was the average time to extubation between sedation groups. Secondary outcomes included ICU length of stay (LOS) and postoperative intravenous (IV) opioid requirements in total morphine milligram equivalents (MME). Results: A total of 168 patients were included, with 93 (55.3%) in the propofol group, and 75 (44.6%) in the dexmedetomidine group. No significant difference was observed in the average time to extubation between propofol and dexmedetomidine [5.5 hours (4-7.4) vs. 5.7 hours (3.9-7.9), p=0.715]. ICU LOS and postoperative IV opioid requirements were not statistically significant between groups [48.3 hours (44-70.7) vs. 47.3 hours (43.7-69), p=0.638] and [32 MME (18-50) vs 32 MME (24-56), p=0.333], respectively. There was no statistical difference in the incidence of adverse events (bradycardia, tachycardia, atrial fibrillation, hypotension, or reintubation) between groups. Conclusions: The study suggests that utilizing dexmedetomidine as the primary sedative agent did not reduce the time to extubation in the postoperative open-heart surgery setting. Although there was no significant difference in the incidence of safety events between groups, the incidence of hypotension and reintubation are numerically higher in the propofol group.