Objectives: Was to evaluate the effect of different regional anesthetics (articaine with epinephrine versus prilo - caine with felypressin) on stress in the extraction of impacted lower third molars in healthy subjects. Sutdy Desing: A prospective single-blind, split-mouth cross-over randomized study was designed, with a control group. The experimental group consisted of 24 otherwise healthy male volunteers, with two impacted lower third molars which were surgically extracted after inferior alveolar nerve block (regional anesthesia), with a fortnight's interval: the right using 4% articaine with 1:100.000 epinephrine, and the left 3% prilocaine with 1:1.850.000 fely - pressin. Patients were randomized for the first surgical procedure. To analyze the variation in four stress markers, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, prolactin and cortisol, 10-mL blood samples were obtained at t = 0, 5, 60, and 120 minutes. The control group consisted of 12 healthy volunteers, who did not undergo either extrac - tions or anesthetic procedures but from whom blood samples were collected and analyzed in the same way. Results: Plasma cortisol increased in the experimental group (multiple range test, P <0.05), the levels being sig - nificantly higher in the group receiving 3% prilocaine with 1:1.850,000 felypressin (signed rank test, p <0.0007). There was a significant reduction in homovanillic acid over time in both groups (multiple range test, P <0.05). No significant differences were observed in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol or prolactin con - centrations between the experimental and control groups. Conclusions: The effect of regional anesthesia on stress is lower when 4% articaine with 1:100,000 epinephrine is used in this surgical procedure.