AIM: Root canal preparation may produce a large quantity of smear layer that covers canal walls. Single-file systems have recently appeared, with the aim of reducing the number of steps and files to reach a correct endodontic treatment. The purpose of this study was to evaluate by SEM the root canal walls after instrumentation with F360 (Komet, Brasseler GmbH & Co., Lemgo, Germany) and F6 Skytaper (Komet, Brasseler GmbH & Co., Lemgo, Germany), in order to evaluate the presence/absence of smear layer and the presence/absence of open tubules on the root canal walls at coronal, middle, and apical third of each sample. METHODS: Twenty single-rooted freshly extracted teeth were selected and divided into 2 groups. For each group root canals were shaped with F360 (Komet, Brasseler GmbH & Co., Lemgo, Germany) and F6 Skytaper (Komet, Brasseler GmbH & Co., Lemgo, Germany) instruments under irrigation with 5,25% NaOCl and 17% EDTA. Specimens were fractured longitudinally and analyzed by SEM at standard magnification of 5000x. The presence/absence of smear layer and the presence/absence of open tubules at the coronal, middle, and apical third of each canal were evaluated using a 5-step scale for scores. Numeric data were analyzed using Kruskall-Wallis and Mann-Whitney U statistical tests and significance was predetermined at P <0.05. RESULTS: This study did not reveal differences among two groups at the coronal and apical third. The apical third showed the highest values of scores for all Ni-Ti systems used. Significant differences in smear layer scores were recorded among the Ni-Ti systems at middle canal level (P < 0.05), where F6 Skytaper showed significantly lower scores than F360. CONCLUSIONS: Within the limitation of this study, F360 and F6 Skytaper rotary instruments seem to be effective in shaping root canals with good debridement from canal walls, without significant differences between the two systems as it regards the coronal third and the apical third, the area where more debris is still visible. Instead, in the middle third F6 Skytaper seems to be more effective than F360, with statistically significative differences between the two systems.