The purpose of this prospective, randomized, double-blind study was to compare the degree of pulpal anesthesia obtained with 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine in inferior alveolar nerve blocks. Using a crossover design, inferior alveolar nerve blocks were randomly administered, in a double-blind manner, using 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine, at two separate appointments, to 57 subjects. A pulp tester was used to test for anesthesia, in 4-min cycles for 60 min, of the molars, premolars, central, and lateral incisors. Anesthesia was considered successful when two consecutive 80 readings were obtained within 15 min and the 80 reading was continuously sustained for 60 min. Using the articaine solution, successful pulpal anesthesia ranged from 4 to 54% from the central incisor to the second molar. Using the lidocaine solution, successful pulpal anesthesia ranged from 2 to 48%. There was no significant difference (p > 0.05) between the articaine and lidocaine solutions. We concluded that 4% articaine with 1:100,000 epinephrine was similar to 2% lidocaine with 1:100,000 epinephrine in inferior alveolar nerve blocks.