Objective To compare the effects of dexmedetomidine and propofol on sedation and hemodynamics of patients undergoing mechanical ventilation after cardiac valve surgery. Methods Sixty patients who received mechanical ventilation after cardiac valve surgery were randomly divided into dexmedetomidine group (Group D, n=30) and propofol group(Group P, n=30). The patients in group D received the sedation formula of dexmedetomidine 0.2-0.7 μg/(kg·h) and sufentanil 0.15 μg/(kg·h), while those in group P received the sedation formula of propofol 1.2-3.0 mg/(kg·h) and sufentanil 0.15 μg/(kg·h). The dose of sedation was regulated in order to maintain bispectral index (BIS) score at 70-85 and Richmond agitation-sedation scale (RASS) at -2——3. Hemodynamic parameters of the patients were assessed at pre-operation (T₁), 2 h post-cardiopulmonary bypass (CPB, T₂), 4 h post-operation (T₃) and 12 h post-operation (T₄). We compared and analyzed the sedation scores of BIS and RASS, and incidences of complications such as mean arterial pressure (MAP) decrease, bradycardia, delirium or agitation of the patients in two groups. Results There was no significant difference between two groups in BIS score and RASS score (P>0.05). There was a significant difference in hemodynamics change between the two groups. The MAP in Group P was significantly lower than that in Group D at T₂ (P<0.05). The cardiac index in Group D was significantly higher than that in Group P at T₃ (P<0.05) and T₄ (P<0.01). Arterial blood lactate contents in Group D were significantly lower than that in Group P at T₂, T₃ and T₄ (P<0.05, P<0.01).There was no significant difference between two groups in systemic vascular resistance index, stroke volume, right ventricular ejection fraction or oxygen saturation of mixed venous blood (P>0.05). The vasoactive agent dosages were not different between two groups (P>0.05). There was no significant difference between two groups in incidences of post-operative MAP decrease or bradycardia (P>0.05) and the incidences of post-operative delirium or agitation in Group D was significantly lower than those in Group P (P<0.05). Conclusion Sedation effect of both drugs is good in our study. Dexmedetomidine has relatively less influence on hemodynamics, and it can reduce the incidence of post-operative agitation or delirium. Dexmedetomidine seems to be more appropriate for post-operative sedation for the patients undergoing mechanical ventilation after cardiac valve surgery.