The purpose of this study was to evaluate in vivo the response of the periradicular tissues after endodontic treatment and root filling with Epiphany/Resilon (Penntron Clinical Technologies, LLC, Wallingford, CT) or
gutta percha and new
Sealapex (SybronEndo, Glendora, CA) in dogs' teeth with or without coronal restoration. Teeth without coronal restorations were used to assess the influence of continuous exposure to the oral environment on the periradicular tissues. Sixty root canals with vital pulps in three dogs were instrumented and obturated in a single session and randomly assigned to one of four groups as follows. group 1: root canal filling with Epiphany/Resilon with coronal restoration, group 2: root canal filling with
Sealapex sealer and
gutta percha with restoration, group 3: root canal filling with Epiphany/Resilon without restoration, and group 4: root canal filling with
Sealapex sealer and
gutta percha without coronal restoration. After 90 days, the animals were euthanized, and the maxillas and mandibles were removed and submitted for histologic processing. Longitudinal sections were obtained and stained with
hematoxylin and
eosin, Mallory's trichrome, and Brown and Brenn stains and examined under light microscopy. There were significant differences found between the four groups (p < 0.05). The results showed that roots canals filled with Epiphany/Resilon, with coronal restoration, had significantly less periradicular
inflammation than roots canals filled with
gutta percha and
Sealapex, with coronal restoration (p = 0.021). No significant difference was observed in the intensity of
inflammation between roots canals filled with Epiphany/Resilon with no restoration and roots filled with
gutta percha and
Sealapex with restoration (p = 0.269). Roots canals filled with
gutta percha and
Sealapex sealer without coronal restoration showed the greatest degree of periradicular
inflammation.