A randomized, controlled trial of 31 healthy volunteers compared 4% articaine with 1:100,000 epinephrine buccal infiltration to buccal plus lingual infiltration of the same dose of drug in achieving pulpal anesthesia of mandibular first molar teeth. Data were compared with efficacy of an inferior alveolar nerve block using 2% lidocaine 1:80,000 epinephrine in a cohort of 27 of the volunteers. Anesthesia was determined using electronic pulp testing. Buccal and buccal plus lingual infiltrations of articaine with epinephrine did not differ in efficacy in obtaining pulpal anesthesia for mandibular permanent first molars (p = 0.17). Efficacy of 4% articaine with epinephrine infiltrations for first molar pulp anesthesia was similar to that of an IANB using lidocaine with epinephrine over a 30-minute study period (96 and 80 episodes of no response to maximal stimulation respectively, p = 0.097). Subjective tooth numbness was more common after IANB than buccal infiltration (p = 0.005). The discomfort of buccal infiltration with articaine was volume dependent (p = 0.017) and similar to that of an IANB.