The aim of the study is to compare the efficacy of anesthesia and hemodynamic parameters of clonidine and epinephrine in lignocaine for lower third molar surgery.Thirty healthy controls with impacted mandibular third molar were randomly selected from both sexes between the age group of 20-47 years. Patients were divided equally into two groups: Group I (Adrenaline group) and Group II (Clonidine group). Patients received 2.5 ml of 2% lignocaine with adrenaline (12.5 μg/ml) in Adrenaline group and 2.5 ml of 2% lignocaine with clonidine (15 μg/ml) in Clonidine group. Hemodynamic parameters (heart rate, systolic blood pressure [SBP], diastolic blood pressure [DBP], and mean arterial pressure [MAP]) were recorded preoperatively, intraoperatively, and postoperatively. The onset of anesthesia and duration of anesthesia were recorded using pinprick test for both groups. Postoperatively, patients were evaluated for pain experience by the visual analog scale and verbal rating scale.Lignocaine with clonidine intraoperatively and postoperatively decreases SBP and DBP and MAP compared to lignocaine with adrenaline. There was no significant difference in the onset and duration of anesthesia in both the groups. There was a statistically significant difference seen in the visual analog scale, but no statistically significant difference was seen in the verbal rating scale.Clonidine has similar efficacy as that of adrenaline with better hemodynamic parameters and can be used as an alternative to adrenaline for third molar surgeries.