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Placement of orifice plugs has been suggested to augment the seal of conventional root canal fillings. This study assessed in vivo the efficacy of white mineral trioxide aggregate (MTA) plugs in preventing periapical inflammation subsequent to coronal inoculation of root-filled teeth. The two-rooted mandibular premolars of six beagle dogs were conventionally prepared and filled with gutta-percha and sealer. A white MTA orifice plug was placed into one canal in each tooth. Pulp chambers were inoculated with plaque except for 12 teeth (negative control), and restored. Radiographs were taken at regular intervals. At 10 months, dogs were killed and jaw blocks processed for histology. None of the roots revealed radiographic or histologic evidence of severe inflammation. Mild inflammation was observed in 17% and 39% of the roots with and without an orifice plug, respectively (McNemar, p > 0.05). Without development of severe inflammation, the seal augmentation efficacy of MTA orifice plugs could not be determined.