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The aim of this in vitro study was to determine the effect of the smear layer on apical and coronal leakage in root canals obturated with AH26 or Roe-koSeal sealers. A total of 160 maxillary anterior teeth extracted for periodontal reasons were used. The root canals were prepared to a size #7 with ProFile .06 taper Series 29 rotary instruments in a crown-down manner. Eight groups were created by all possible combinations of three factors: smear layer (present/absent), leakage assessment (apical/coronal), and sealer used (AH26/Roeko-Seal). All teeth were obturated using lateral condensation technique of gutta-percha. A fluid filtration method was used to test apical or coronal leakage. According to the results of this study, the smear (+) groups displayed higher apical and coronal leakage than those smear (−) groups for both root canal sealers (p < 0.05). There was no statistically significant difference in either apical or coronal leakage between RoekoSeal and AH26, regardless of the presence or absence of the smear layer (p > 0.05). However, apical leakage was significantly higher than coronal leakage for both root canal sealers used in this study (p < 0.05). Under the conditions of this study, the results indicate that removal of the smear layer has a positive effect in reducing apical and coronal leakage for both AH26 and RoekoSeal root canal sealers.