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Aim The study compared the anesthetic effectiveness of articaine and lignocaine when premolars are extracted bilaterally for orthodontic purposes. Material and methods This prospective split-mouth study was performed on 30 cases selected from orthodontic referral patients reporting to the Oral and Maxillofacial Surgery Department at Maharaja Ganga Singh Dental College and Research Center, Rajasthan, India, for bilateral extraction of premolars under local anesthesia. We used 4% articaine hydrochloride and adrenaline 1:100000 (AH) as group A and 2% lignocaine hydrochloride with adrenaline 1:100000 (LH) on the control side as group B. For premolar anesthetization, 0.6-1.6 ml of AH and 1-2 ml of LH were injected submucosally in the buccal vestibular area. The extraction procedure was then carried out after achieving adequate anesthesia. The pain was assessed with Visual Analog Scale. The average onset time and duration of anesthesia were recorded. Data collected were summarized with descriptive statistics. The SPSS version 23.0 (IBM Corp., Armonk, New York) was used for data entry, validation, and analysis. Means of continuous variables were compared using the student t-test. All tests were 2-tailed and significant at equal or less than 0.05. (p≤0.05). Results When comparing the overall anesthetic efficiency, Group A had a lower overall pain score of 0.43 while Group B had a higher overall pain score of 2.9. The average onset time of anesthesia in Group A was 1.2 minutes and 2.55 minutes in Group B. In Group A, the average duration of anesthesia was 70 minutes, and 46.5 minutes in Group B. These parameters were statistically significant with a p-value of <0.05. Conclusion The study concluded that as an alternative to lignocaine, articaine could be used effectively for maxillary premolar extractions for orthodontic reasons obviating palatal injection which is very painful to the patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jaiswal et al.)