Background: Optimal sedation management for mechanically ventilated (MV) patients in the intensive care unit (ICU) remains essential for patient care. Objective: Thisstudy aimedto compare the hemodynamic effects of ketamine and propofol on patient population. Patients and methods: This parallel randomized controlled blind trial was conducted at Menoufia University Hospital, Egypt through the periode from October 2022 to October 2023. The study screened 145 mechanically ventilated ICU patients and only 100 patients who were randomized into two groups (50 in each group) and received continuous infusion sedation with either ketamine (Ketamin group) or propofol (Propofol group) for at least 48 hours. Baseline characteristics, sedation levels, pain control, and hemodynamic parameters were assessed. Results: Baseline characteristics were similar between ketamine and propofol groups. Ketamine resulted in slightly higher heart rates at 45 minutes (80.08 ± 9.18 vs. 75.78 ± 8.92, p = 0.019) and 2 hours (77.42 ± 9.52 vs. 73.42 ± 9.33, p = 0.036). Mean arterial blood pressure was also slightly higher with ketamine at 45 minutes (85.8 ± 8.57 vs. 80.96 ± 9.83, p = 0.010) and throughout 48 hours. However, sedation scores and pain assessments were similar between groups, indicating comparable patient comfort. Ketamine showed lower incidences of hypotension (22% vs. 42%, p = 0.032) and bradycardia (2% vs. 14%, p = 0.027) but higher acute hypertension (38% vs. 16%, p = 0.013) compared to propofol, suggesting a different safety profile. Conclusion: This study provided evidence of the hemodynamic advantages of ketamine over propofol in ICU sedation for MV patients. Ketamine's ability to maintain stable cardiovascular parameters with fewer adverse events suggests its potential as an alternative sedative in this population. Further research is warranted to confirm these findings and optimize sedation strategies in critical care settings.