The purpose of this prospective, randomized, double-blind crossover study was to evaluate the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine in maxillary lateral incisors and first molars. Eighty subjects randomly received, in a double-blind manner, maxillary lateral incisor and first molar infiltrations of one cartridge of 4% articaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine at two separate appointments spaced at least 1 week apart. In maxillary lateral incisors, articaine exhibited a significantly higher anesthetic success rate of 88% when compared with a 62% success rate with lidocaine. In maxillary first molars, articaine had a similar success rate to lidocaine (78% vs 73%), and there was no significant difference between the two solutions. In conclusion, a maxillary infiltration of 4% articaine with 1:100,000 epinephrine statistically improved anesthetic success when compared with 2% lidocaine with 1:100,000 epinephrine in the lateral incisor but not in the first molar.