Objective:To investigate the speed of action and injection discomfort of 4% articaine and 2% mepivacaine for upper teeth extractions.Materials and Methods:Forty-five patients were included in the articaine 4% group, and 45 in the mepivacaine 2% control group. After all injections, soft and hard tissue numbness was objectively gauged by dental probe at intervals of 15 s. Furthermore, the discomfort of the injections were recorded by the patients after each treatment on standard 100 mm visual analog scales, tagged at the endpoints with “no pain” (0 mm) and “unbearable pain” (100 mm).Results:There were significant differences in the meantime of first numbness to associated palatal mucosa and tooth of patients between mepivacaine and articaine buccal infiltration (BI) groups P = 0.01 and 0.01. Patients in the articaine group recorded earlier palatal mucosa and teeth numbness than those in the mepivacaine group. With regards to the discomfort of the needle injections, palatal injection was significantly more painful than BI (t-test: P < 0.001). Articaine buccal injection was significantly more painful than mepivacaine buccal injection (t-test: P <0.001). However, articaine palatal injection was less painful than articaine BI. Clinically, anesthesia onset time was faster in anterior upper teeth than upper middle and posterior teeth.Conclusions:BIs with 4% articaine was faster in achieving palate and teeth anesthesia than 2% mepivacaine for extraction of upper maxillary teeth. Patients in mepivacaine BI and articaine palatal injection groups reported less pain with needle injection. Failure of anesthesia was noticeable with maxillary multiple-rooted teeth.