A randomized, double-blind trial was conducted to compare the efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine when used as a supplemental anesthetic. Forty-eight patients with irreversible pulpitis requiring supplemental buccal infiltration for endodontic therapy were given either 4% articaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine in a double-blind manner. A standard VAS pain scale was used to evaluate the patient's response to pain after a supplemental injection. The mean VAS score after supplemental anesthesia was 15.28 for 4% articaine with 1:100,000 epinephrine and 19.70 for 2% lidocaine with 1:00,000 epinephrine. The mean percentage change in VAS score was 70.5 and 62.2% for articaine and lidocaine, respectively. There was no statistically significant difference in the VAS pain score between 4% articaine with 1:00,000 epinephrine and 2% lidocaine with 1:00,000 epinephrine as a supplemental anesthetic.