Background: Weaning from mechanical ventilation (MV) is a major challenge in the intensive care unit (ICU). We evaluated the use of dexmedetomidine to reduce the duration of weaning, compared standard sedation protocols. Methods: Single-centre, retrospective, observational study in a mixed ICU from April 2018 to April 2020. All patients aged ?18 years, requiring MV for at least 5 days before initiation of a weaning protocol, were eligible for inclusion. Patients were grouped retrospectively according to whether they received dexmedetomidine or standard sedation for weaning. The primary endpoint was the average duration (in hours) of weaning from MV. Secondary endpoints were the frequency of self-extubation, and occurrence of re-intubation within 48 hours. A propensity score was used for the analysis of the primary endpoint. Results: Among 1132 patients admitted during the study period, 112 were included: 66 in the standard care group, and 46 in the dexmedetomidine group. The duration of weaning did not differ significantly between groups (104.8 hours in the standard care group versus 127.1 hours in the dexmedetomidine group, p=0.1552). Self-extubations were numerically albeit non-statistically significantly more frequent in the standard care group (n=6 (9.09%) vs n=2 (4.54%)) with dexmedetomidine, p=0.3481). Similarly, re-intubation was also numerically more frequent in the standard care group, albeit without reaching statistical significance (n=5 (8,20%) vs n=1 (2.22%) with dexmedetomidine, p=0.1234). Conclusion: The duration of weaning from MV is numerically, but not statistically significantly shorter with standard care as compared to weaning facilitated by dexmedetomidine.