In order to compare the efficacy of lidocaine and articaine for pain control during third molar surgery, 160 patients presenting bilateral asymptomatic impacted mandibular third molars were selected. They received 1.8 mL of 2% lidocaine with epinephrine 1:100,000 during inferior alveolar nerve block. In group 1 (n = 80), an infiltrative injection of 0.9 mL of 2% lidocaine with epinephrine 1:100,000 was performed in buccal-distal mucosa of the third molar. Group 2 (n = 80) received 0.9 mL of 4% articaine with epinephrine 1:100,000 in the contralateral side. All procedures were performed at the same visit, by a single operator, in a double-blind and parallel design. The duration of each surgery and the moment when the patient expressed pain were noted. Data were analyzed by nonpaired t test and chi-square test (alpha = 5%). Duration of surgery did not differ (p = .83) between Groups 1 (19.8 ± 2.3 minutes) and 2 (19.7 ± 3.0 minutes). Pain was expressed more in group 1 (26.3%) than in group 2 (10%) (odds ratio = 3.2, p = .0138). In both groups, tooth sectioning was the most painful event (p < .0001). No influence of gender (p = .85) or age (p = .96) was observed in pain response. Buccal infiltration of 4% articaine with epinephrine 1:100,000 showed more efficacy than 2% lidocaine with epinephrine 1:100,000 when used in combination with inferior alveolar nerve block in controlling intraoperative pain related to impacted mandibular third molar surgery.