We conducted a single blinded prospective study on infiltration anesthesia using articaine in the muco-buccal fold opposite the impacted lower third molar and the purpose of this study was to evaluate the clinical anesthetic efficacy of buccal infiltration obtained by 3.4 ml of 4% articaine (with 1:100,000 epinephrine) in extraction of impacted mandibular third molar with supplemental lingual anesthesia. For the purpose of study 54 patients of impacted mandibular third molar were included. All surgical procedures were performed by a single surgeon, who began the procedure after buccal infiltration of 3.4 ml of 4% articaine (with 1:100,000 epinephrine) in the muco-buccal fold opposite the impacted lower third molar with supplemental lingual anesthesia. For assessment of anesthetic efficacy, any pain during surgery was recorded using the visual analog scale. Also, the onset and duration, anesthesia were recorded. Data was analyzed using statistical package of social sciences (SPSS) software. Buccal infiltration of articaine, as a sole anesthetic technique in surgical removal of impacted lower third molar achieved successful anesthesia in 92.5% of our study patients. Thus, the results of this present study may be enough evidence to support the view that using 4% articaine (with 1:100,000 epinephrine) infiltrations in the muco-buccal fold opposite the impacted lower third molar may be a good option for lower third molar surgery with supplemental lingual anesthesia.