Objective: The purpose of the study is to compare the effects of lidocaine alone, epinephrine-combined lidocaine and prilocaine with octapressin on the cardiovascular system during minor oral surgery of sedated cardiac dental patients under local anesthesia. Materials and Methods: Connected to a Holter electrocardiogram (ECG) monitor for a total of 5 hours starting 1 hour before the procedure, twenty patients with high risk of coronary artery disease were included in the prospective cohort study. All the patients had three operations at 3 different appointments with at least one-week intervals and each operation was performed under local anesthesia achieved by 3.6 mL of 3% prilocaine with octapressin, 3.6 mL of 2% lidocaine with 1: 80.000 epinephrine and 3.6 mL of 2% lidocaine without a vasoconstrictor. Data of the Holter ECG device assessed at the end of every hour and evaluated statistically. Repeated measures ANOVA, Friedman test, and Wilcoxon signed ranks test were used to perform statistical analysis. Results: Heart-rate showed significant differences between lidocaine with epinephrine and pure lidocaine in an hour following the injection (p<0.05 for all). Cardiac rhythm showed significant differences between prilocaine with octapressin and pure lidocaine at the second hour after its administration (p<0.05 for all). There were no significant differences between 3 local anesthetics in terms of ST segment deviation. Conclusion: In minor oral operation on the sedated patients with cardiac disease, the use of 3.6 mL or a less amount of local anesthetic injection containing epinephrine appears to be a predictable and safe method.