Aim <p>This clinical trial is conducted to assess the efficacy and safety of 4% articaine in inferior alveolar nerve block after surgical removal of Mandibular 3rd molar. The comparison was made with 2% Mepivacaine.</p> Methods <p>This is a double blind clinical trial. 25 patients with bilateral mandibular impaction were selected to be the sample size. 4% Articaine with 1:2,000,000 Adrenaline was used on the first side of the patient for inferior alveolar nerve block before the surgical removal of the impacted tooth. And the same patient was operated for the other side with 2% Mepivacaine with 1:2,000,000 Adrenaline after a gap of 2 to 3&#xa0;weeks.</p> Results <p>Data from a total of 25 patients, 17 (68%) males and 08 (32%) females represented the Articaine and Mepivacaine groups. The patient's mean age was 24.12 ± 4.859&#xa0;years. The anesthesia onset time taken was delayed in the Mepivacaine group (2.45 ± 1.152) in comparison with the Articaine group (1.51 ± 0.756) minutes which was statistically significant (p = 0.001). The duration of pain-free hours and the need for the first analgesic was reported to be more in the Articaine group (1.76 ± 1.088) than the patients in the Mepivacaine group (1.64 ± 0.736) which was statistically non-significant (p = 0.476). Satisfaction was rated better in the Mepivacaine group (4.75 ± 0.957 vs 4.25 ± 0.779) which was statistically non-significant (p = 0.723). 5 patients developed inferior alveolar nerve paresthesia in articaine group but recovered by the end of 4th week. There was no statistically significant difference between the groups with respect to pain, patient satisfaction and other vital parameters.</p> Conclusion <p>The Articaine has faster onset of action than Mepivacaine.The duaration of anaesthesia and intensity is similar in both groups. But despite similar efficacy in pain relief, the 20% transient paresthesia rate according to our data makes articaine less safe and less preferred than mepivacaine.</p>