BACKGROUND: This prospective, randomized, double-blind, clinical study was conducted to compare the effects of 4% articaine with 1:100,000 epinephrine (A100) and 4% articaine with 1:200,000 epinephrine (A200) on the vital signs and onset and duration of anesthesia in an inferior alveolar nerve block (IANB). METHODS: In the first appointment, an IANB was performed by injecting A100 or A200 in 1 side of the mouth (right or left) randomly in patients referred for extraction of both their first mandibular molars. In the second appointment, the protocol was repeated and the other anesthetic solution was injected in the side that had not received the block in the previous session. Systolic and diastolic blood pressures (SBP and DBP) and pulse rate were measured during and 5 min after the injection. The onset and duration of anesthesia were also evaluated. Data were analyzed using t-test and Mann-Whitney U-test, and p-value was set at 0.05. RESULTS: SBP and pulse rate changes were slightly more with A100; however, DBP changes were more with A200, although the differences were not significant (P > 0.05). There were no statistically significant differences in the parameters evaluated in this study. The onset and duration of anesthesia, and the changes in SBP, DBP, and pulse rate during and 5 min after the injection were the same in both the groups. CONCLUSIONS: For an IANB, A200 and A100 were equally efficient and successful in producing the block. Epinephrine concentration did not influence the effects of 4% articaine.