Background: The purpose of the study was to compare the efficacy of 0.5% centbucridine and 2% lignocaine with adrenaline (1:200,000).Methods: A clinical prospective, controlled, randomized, double blind group study was conducted on 22 patients referred for extraction of mandibular premolars, who were randomly assigned to 2 groups by the split mouth method. Before extraction of mandibular premolar, either 0.5% centbucridine or 2% lignocaine with 1:200,000 adrenaline were used for anesthesia. All the patients were given inferior alveolar, lingual, and long buccal nerve blocks. Pain on injection, onset of anesthesia, duration of anesthesia and changes in blood pressure and pulse rate were monitored and recorded.Results: In our study, statistically significant difference was found between the efficacy of agents as for time for onset of anesthesia, duration of action, and changes in blood pressure and pulse rate, but no statistically significant difference was found for pain on injection between two groups.Conclusions: The efficacy of centbucridine was found to be more as compared to lignocaine with adrenaline, in rapid onset of anesthesia, longer duration of action, and cardiovascular stability. There was no significant difference in the pain on injection for both centbucridine and lignocaine with adrenaline. Centbucridine can be used in medically compromised condition where adrenaline is contraindicated.