Objective · To compare the efficacy and safety of oral premedication with midazolam (MID), ketamine (KET), and dexmedetomidine (DEX) in children with tetralogy of Fallot (TOF). Methods · Sixty children undergoing selective primary repair for TOF were randomly assigned to orally receiving MID (0.5 mg/kg, Group M), KET (5 mg/kg, Group K), and DEX (5 μg/kg, Group D) with twenty children in each group. The acceptance of administration, HR, SpO2, and sedation score before administration and at different time points after administration, scores of separation and intravenous cannulation 30 min after administration were observed and recorded. Results · The acceptance of administration was significantly higher in Group D than in other two groups (P<0.05). There was no significant difference in sedation onset time among three groups (P>0.05). The satisfaction rates of separation and intravenous cannulation were significantly higher in Group K than in Group D and Group M (P<0.05). There were no significant differences between HR and SpO2 at different time points after administration and baseline values before administration in three groups. Conclusion · Oral premedication with MID, KET, and DEX can provide good sedation for children with TOF. Children receiving oral KET have the highest satisfaction rates of separation and intravenous cannulation.