Objective: The third molar extraction is one of the most common surgical procedures in oral surgery and is usually accompanied by postoperative discomfort. It has been suggested that the longer duration of action of bupivacaine associated with the residual analgesia and the gradual onset of pain, could decrease the need for analgesics during the postoperative period. This study aims to compare the efficacy and safety of bupivacaine and articaine as local anesthetics for the extraction of mandibular third molars and to check whether bupivacaine produced residual analgesia. Study design: We compared bupivacaine 0.5% and articaine 4% with an epinephrine concentration of 1:200 000 in a crossover design model of extraction of bilaterally symmetrical mandibular third molars. Results: Regarding efficacy, patients experienced less postoperative pain at 6 and 12 hours and shorter duration of soft tissue anesthesia with articaine. With respect to safety, no differences were found between the anesthetics compared, showing a similar local and systemic toxicity. With regard to the preference of patients, it was higher for articaine, the main reasons being the greater postoperative pain and swelling with bupivacaine. Conclusion: It can be concluded that articaine seems to be a more appropriate anesthetic for the extraction of mandibular third molars due to the shorter duration of the anesthetic effect in the soft tissues, lower pain reported by patients during the immediate postoperative period and the personal preference of patients for this drug.