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Objectives: Meta-analysis was used to quantitatively synthesize results from clinical studies comparing four percent articaine hydrochloride to two percent lidocaine hydrochloride, both with epinephrine 1:100,000. The null hypothesis was that there is no statistically significant difference in efficacy of the two anesthetic agents. Methods: Potential studies for inclusion were identified using the MeSH database search terms carticaine (articaine MeSH term) and lidocaine in a PubMed search. Inclusion criteria included randomized clinical trials in humans with a clear determination of anesthetic efficacy with respect to initial administration of these two anesthetic agents in dental applications. Twelve randomized, clinical trials met the inclusion criteria. The overall approach of this meta-analysis emphasized the pulpal anesthetic success (by means of electric pulp test and/or visual analog scale for intra-operative pain); secondary analyses evaluated timelines of pulpal anesthesia. The combined results for percentage of teeth achieving pulpal anesthetic success were based on the reported data from ten suitable studies, using the Fisher meta-analytic method of combining significance probabilities. Results: Individually, two of these studies reported significantly superior performance of articaine hydrocholoride compared to lidocaine hydrochloride on the basis of achievement of pulpal anesthetic success; a third study reported a suggestive result (p=0.057). In four additional studies, the observed rate of anesthetic success was greater for articaine hydrocholoride, although not significantly so; the performance of the two anesthetic agents was identical in the remaining three studies. Differences in anesthetic success based upon tooth type/location and injection type were explored. Further results were obtained for pulpal anesthetic timelines. Conclusions: The overall result for anesthetic success based upon meta-analysis by the Fisher method was that articaine hydrochloride demonstrated statistically superior efficacy (p=0.004) relative to lidocaine hydrochloride. Supported by the University of Iowa Department of Endodontics.