Background: Third molar extraction is the most commonly performed minor oral surgical procedure in outpatient settings and requires regional anesthesia for pain control. Extraction of the maxillary molars commonly requires both posterior superior alveolar nerve block (PSANB) and greater palatine nerve block (GPNB), depending on the nerve innervations of the subject teeth. We aimed to study the effectiveness of PSANB alone in maxillary third molar (MTM) extraction. Methods: A sample size comprising 100 erupted and semi-erupted MTM was selected and subjected to study for extraction. Under strict aseptic conditions, the patients were subjected to the classical local anesthesia technique of PSANB alone with 2% lignocaine hydrochloride and adrenaline 1:80,000. After a latency period of 10 min, objective assessment of the buccal and palatal mucosa was performed. A numerical rating scale and visual analog scale were used. Results: In the post-latency period of 10 min, the depth of anesthesia obtained in our sample on the buccal side extended from the maxillary tuberosity posteriorly to the mesial of the first premolar (15%), second premolar (41%), and first molar (44%). This inferred that anesthesia was effectively high until the first molars and was less effective further anteriorly due to nerve innervation. The depth of anesthesia on the palatal aspect was up to the first molar (33%), second molar (67%), and lateromedially; 6% of the patients received anesthesia only to the alveolar region, whereas 66% received up to 1.5 cm to the mid-palatal raphe. In 5% of the cases, regional anesthesia was re-administered. An additional 1.8 ml PSANB was required in four patients, and another patient was administered a GPNB in addition to the PSANB during the time of extraction and elevation. Conclusion The results of our study emphasize that PSANB alone is sufficient for the extraction of MTM in most cases, thereby obviating the need for poorly tolerated palatal injections.