This report describes a case of sodium hypochlorite (NaOCl) and chlorhexidine (CHX) extrusion through the apical foramen, causing acute pain, swelling and mucosal fenestration. A 62-year-old woman was referred for endodontic treatment in the first left maxillary premolar with a diagnosis of necrotic pulp. After the root canal irrigation with 2.5% NaOCl, the patient felt a burning sensation and pain. Discrete swelling and redness were noted in the patient's face at the end of the session. Antibiotic and corticosteroids were prescribed. In the next appointment, 2% CHX was used, but another episode of extrusion occurred, with a sudden acute pain and intense swelling within a few minutes after the injection. After 2 weeks, the patient exhibited a left-side facial swelling extending anterior and inferior to the left zygomatic arch and superior to the body of the mandible. Oral antibiotic and anti-inflammatory drugs were administered. After 10 days, the swelling had completely diminished, but a mucosal fenestration and tooth mobility were verified. A cone beam CT was requested and showed a periapical lesion involving both buccal and palatal roots. After a prosthetic evaluation, the tooth extraction was indicated. One week after tooth removal, the mucosa was completely healed.