Background/Objectives: An effective inferior alveolar nerve block (IANB) is critical for mandibular third molar surgery, especially for novice student operators who face steep learning curves. This study compared the clinical efficacy and safety of 4% articaine, 2% lidocaine, and 2% mepivacaine in an undergraduate setting. Methods: A prospective observational study was conducted with 189 patients undergoing third molar surgery performed by dental students. Patients received either 4% articaine (n = 69), 2% lidocaine (n = 61), or 2% mepivacaine (n = 59). Anesthetic efficacy was evaluated using a two-stage assessment comprising Vincent’s sign (Stage 1) and profound surgical anesthesia (Stage 2). Intra- and postoperative pain, anesthetic volume, surgical duration, and postoperative complications were recorded and compared among anesthetic groups. Results: Baseline demographics, impaction patterns, and difficulty indices did not differ significantly among groups. Stage 2 profound success rate was significantly higher with articaine (76.8%) than with lidocaine (55.7%) and mepivacaine (61.0%) (p = 0.031). Articaine was also associated with a longer duration of anesthesia (261.7 vs. 164.6
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