The purpose of this study was to compare the effects of ultrasonication with ethylenediaminetetraacetic acid (EDTA) and a mixture of tetracycline isomer, an acid, and a detergent (MTAD) as final canal irrigants on the smear layer, debris and erosion scores. Fifty-eight extracted single-rooted human teeth were instrumented with ProTaper rotary files up to size F3. According to the final irrigation regimen, the samples were distributed into the following groups: EDTA, MTAD, EDTA ultrasonicated for 1 min, and MTAD ultrasonicated for 1 min. The smear layer, debris and erosion scores were recorded at the apical, middle, and coronal third of each canal using a scanning electron microscope. Data were subjected to statistical evaluation using the Kruskal-Wallis and Mann-Whitney tests (P < 0.05). There were no significant differences in smear layer or debris removal between the experimental groups. EDTA caused significantly more erosion at the middle level than MTAD. Also EDTA resulted in more erosion at the coronal level than MTAD when subjected to ultrasonication. Ultrasonic activation of EDTA significantly increased its erosive effects at the middle and coronal levels. Based on the present findings, MTAD appears to cause less dentinal erosion while allowing proper removal of the smear layer and debris.