The number of appointments necessary to treat infected root canals is one of the most controversial issues in endodontics. This study evaluated, in dogs, the response of the periradicular tissues to the endodontic treatment of infected root canals performed in a single visit or in two visits, using different interappointment dressings. Periradicular lesions were induced by inoculating Enterococcus faecalis in the root canals. After confirming that a periradicular lesion developed, the root canals were treated within one or two visits, using either ozonized oil or calcium hydroxide in camphorated paramonochlorophenol (CMCP) as an intracanal medication. After 6 months, the animals were sacrificed and the specimens were processed for histological and histobacteriological analysis. The root canals treated in a single visit showed a success rate of 46%. When a calcium hydroxide/CMCP-based interappointment intracanal medication was used, 74% of the cases were categorized as success. In cases where ozonized oil was used as the intracanal medication, a success rate of 77% was observed. These results of the present study demonstrated that the two-visit treatment offered a higher success rate compared to one-visit therapy. In addition, ozonized oil may potentially be used as an intracanal medication.