Background: Mandibular third molar removal is the most common surgical procedure encountered in oral and maxillofacial clinics. It also presents the greatest challenges and controversies for surgeons when surgical removal is considered. Furthermore, diverse anesthesia results and success rates are achieved after using the same concentrations of different solutions or the same amounts of local anesthetics. The purpose of this study was to examine the efficiency of using double-cartridge (3.4 ml) 4% lidocaine (high concentration) and 4% articaine with a 1:100000 epinephrine infiltration in the retromolar region for impacted lower third molar surgery. Methods: This double-blind study included 30 patients with symmetrically impacted lower third molars. The patients were randomly selected to receive 4% articaine on one side and 4% lidocaine on the other, as a local anesthetic for third molar surgery. The onset, duration of soft-tissue numbness, pulpal sensitivity, amount of additional local anesthetic needed, pain score during the surgical procedure, and duration of the operation were recorded. Results: The results of this research indicate that 86.7% of the operations in the 4% articaine group and 83.3% of those in the 4% lidocaine group were successful. Furthermore, the outcomes in both groups were not statistically significant (P > 0.05). Numbness onset occurred faster in the articaine group than it did in the lidocaine group. However, the duration of soft-tissue anesthesia and pain scores recorded immediately postoperatively were similar. Conclusion It is concluded that 4% lidocaine and 4% articaine had a similar infiltration efficacy in the retromolar region and both local anesthetics are adequate for impacted lower third molar surgery. There were no statistically significant differences between the two local anesthetics regarding pain control and the duration of soft-tissue numbness during the procedure.