Objective To observe the sedative effects of Midazolam combined with Remifentanil versus Propofol combined with Remifentanil in elderly patients with severe cerebral hemorrhage undergoing mechanical ventilation. Methods A total of 75 elderly patients with severe intracerebral hemorrhage who met the inclusion and exclusion criteria and were admitted to Longnan City First People's Hospital from January 2023 to February 2025 were collected. They were divided into an observation group (40 cases) and a control group (35 cases) based on the use of different sedative drugs. Both groups received Remifentanil for analgesia. On this basis, the control group patients received Midazolam for sedation, while the observation group received Propofol for sedation. The sedative effect, hemodynamic indicators, blood gas indicators at different time points after medication, the incidence of ventilator-associated pneumonia, and the incidence of adverse reactions between the two groups were compared and analyzed. Results There was no significant difference in the Behavioral Pain Scale (BPS) scores and Richmond Agitation-Sedation Scale (RASS) scores between the two groups at different time points (2, 8, 24, and 48 hours after medication). The heart rate of the observation group was lower than that of the control group at all time points. There was no significant difference in systolic blood pressure between the two groups at different time points, and no significant difference in diastolic blood pressure in the observation group at 24 and 48 hours; however, the diastolic blood pressure in the observation group at 2 and 8 hours was lower than that of the control group. There was no significant difference in the incidence of ventilator-associated pneumonia and vomiting between the two groups, but the incidence of bradycardia and hypotension was higher in the observation group than in the control group. Conclusion Both midazolam and propofol can meet the sedation requirements of elderly patients with severe cerebral hemorrhage undergoing mechanical ventilation. The midazolam group has little effect on blood gas indicators and hemodynamics, and the overall incidence of adverse events should not be low. It is an ideal sedation mode for elderly patients with severe cerebral hemorrhage undergoing mechanical ventilation.