To evaluate the effects of propofol-based and dexmedetomidine-based sedation regimens on achieving early extubation, length of stay (LOS), intensive care length of stay (ICU-LOS), total hospital costs, and mortality rates in cardiac surgery patients. Twenty-three-month retrospective analysis. Single center, 907 bed community teaching hospital. Five hundred eighty-two patients ≥ 18 years of age who received propofol-based or dexmedetomidine-based sedation after cardiac valve or coronary artery bypass grafting (CABG) surgery and who did not undergo prolonged surgery (≤ 8 hours). Retrospective review of medical records. Baseline characteristics (eg, age, sex, comorbidities) and outcomes (eg, achievement of early extubation, LOS, ICU-LOS, total hospital costs, pharmacy costs) were collected. Early extubation was achieved more frequently in the dexmedetomidine group when compared with the propofol group (68.7% v 58.1%, p = 0.008). The mean postoperative time to extubation and hospital LOS were shorter in the dexmedetomidine group when compared with the propofol group (8.8 v 12.8 hours, p = 0.026) and (181.9 v 221.3 hours, p = 0.001), respectively. There was a reduced ICU-LOS in the dexmedetomidine group compared with the propofol group that did not reach statistical significance (43.9 v 52.5 hours, p = 0.067). Average total hospital charges for the dexmedetomidine group were approximately $4000.00 less than the propofol group. Dexmedetomidine-based sedation resulted in achievement of early extubation more frequently than propofol-based sedation. Mean postoperative time to extubation and average hospital LOS were shorter with dexmedetomidine-based sedation and met a statistical level of significance. There was no difference in ICU-LOS or in-hospital mortality between the two groups. Total hospital charges were similar, although slightly higher in the propofol group.