Mucous membrane pemphigoid (MMP) is a heterogeneous group of chronic autoimmune subepithelial blistering diseases. Oral involvement is present in almost all patients, may represent the onset of the disease, and causes different degrees of pain, dysphagia, soreness, and bleeding. Treatment is based on systemic and/or oral corticoids, or other immunosuppressants. Occasionally, oral lesions can show a poor response to standard treatments. We present the case of a 61-year-old female patient with a painful extensive MMP oral ulcerative lesion recalcitrant to previous systemic azathioprine and local triamcinolone treatment, which was successfully treated in a novel way using PRGF infiltrations as adjuvant. After four weekly infiltrations, pain was reduced from 10 to 0 in a VAS and the lesion was completely healed. The patient continued with a low dose maintenance immunosuppressive treatment (prednisone 5 mg/day PO), and after 13 months of follow-up, there was no relapse of the lesion and no side effects. Although future research is necessary to confirm these observations, PRGF could be a useful adjuvant for the management of extensive mucous membrane pemphigoid oral lesions.