The purpose of this study was to determine anesthetic success in adjacent teeth following a primary infiltration of the maxillary lateral incisor and first molar using 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. Three hundred eight asymptomatic subjects received an infiltration of a cartridge of 2% lidocaine with 1:100,000 epinephrine over the maxillary lateral incisor (163 subjects) or first molar (145 subjects). Pulpal anesthesia of the injected tooth and adjacent mesial and distal teeth was monitored with the electric pulp tester in 2-minute cycles for a total of 60 minutes. No response from the subject at the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Comparisons of the odds of pulpal anesthesia (defined as an 80/80 response to electric pulp testing over 60 minutes) between the experimentally injected tooth and adjacent teeth were analyzed using mixed-models, repeated-measures logistic regression. When compared with the lateral incisor infiltration, the adjacent mesial tooth (central incisor) and distal tooth (canine) achieved statistically lower anesthetic success. When compared with the first molar, the mesial tooth (second premolar) did not differ statistically. However, significant differences were shown between the first molar and the second molar, with the distal tooth (second molar) achieving a statistically higher rate of pulpal anesthesia, which was related to a better duration of anesthesia. For asymptomatic patients, local anesthesia of the adjacent mesial (central incisor) and distal (canine) teeth to the infiltrated lateral incisor had lower pulpal anesthetic success. Because standard infiltration anesthesia of the lateral incisor is of short duration, repeating the infiltration at 30 minutes will result in a high incidence of pulpal anesthesia for 60 minutes. Local anesthesia of the adjacent distal tooth to the first molar (second molar) had a statistically higher rate of total pulpal anesthesia than the infiltrated first molar due to the longer duration of pulpal anesthesia. However, if pulpal anesthesia is required for 60 minutes in the first and second molars, the clinician may need to add an additional infiltration to ensure anesthesia.