The purpose of this prospective, randomized, blinded study was to determine the anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection using the computer-assisted Wand Plus injection system versus a conventional syringe. The authors, using a crossover design, randomly administered in a blind manner 2 AMSA injections utilizing the computer-assisted injection system and a conventional syringe to 40 subjects during 2 separate appointments. A pulp tester was used to test for anesthesia, in 4-minute cycles for 60 minutes, of the central and lateral incisors, canine, and first and second premolars. Anesthesia was considered successful when 2 consecutive no responses (80 readings) with the pulp tester were obtained. For all teeth, except the central incisor, the use of the computer-assisted injection system was significantly (P < .05) more likely to result in pulpal anesthesia than the use of the conventional syringe technique. For the computer-assisted injection system, successful pulpal anesthesia ranged from 35 to 58%, and for the conventional syringe, successful pulpal anesthesia ranged from 20 to 42%. For both techniques, the onset of pulpal anesthesia was slow, and duration of pulpal anesthesia declined steadily over 60 minutes. We conclude that although the AMSA injection using the computer-assisted injection system was more successful than the conventional syringe technique, the rather modest to low success rates, slow onset, and declining duration of pulpal anesthesia over 60 minutes would not ensure predictable pulpal anesthesia from the second premolar to the central incisor.