Background: Complications following impacted third molar surgery significantly affect patients’ quality of life during the immediate postoperative period. This study aimed to achieve the proper anesthesia method by comparing the effect of the application of lidocaine alone with the application of lidocaine and articaine simultaneously in reducing the complications during and following impacted mandibular third molar surgery. Methods: The study design was a split-mouth double-blind randomized clinical trial. The study was conducted on 13 patients (26 samples) referred for elective surgical removal of bilateral impacted mandibular third molar with similar difficulty on both sides. Each patient underwent similar surgical procedures on two separate appointments. Each patient randomly received 2% lidocaine for conventional inferior alveolar nerve block and 4% articaine for local infiltration before the surgery on one side (group A) and 2% lidocaine alone (for both block anesthesia and infiltration) before the surgery on the other side (group B). Intraoperative and postoperative variables for both groups were established and statistically analyzed. Results: The findings showed that pain on the first day after surgery in group A was significantly lower than that in group B. The patients in group A mentioned experiencing less discomfort following the surgery. The increased horizontal swelling on the first and third days following surgery and oblique swelling on the seventh day in patients in group B were statistically significant. Conclusion Choosing an appropriate anesthetic drug for oral surgery, specifically impacted third molar surgery, is dependent on the clinician’s opinion, however; it seems that the combination of lidocaine and articaine may control the patient’s pain significantly better than lidocaine alone.