Background Pemphigus vulgaris (PV) is a potentially fatal autoimmune, vesiculobullous, mucocutaneous disease. Recalcitrant oral lesions of PV can result in significant oral discomfort and interfere with eating and oral hygiene. Increasing the dosage of systemic medications to control such lesions results in higher risk of side effects. Currently, there is 1 published report describing 2 patients with healing of oral recalcitrant lesions after carbon dioxide (CO2) laser vaporization. Case Summary We describe here a case of a 51-year-old male patient diagnosed with PV through biopsy and direct immunofluorescence in 2013. At baseline, the patient had a history of premature ventricular contractions, allergy to penicillin, occasional alcohol intake, and no tobacco use. He was on analgesics for mouth pain. After further baseline laboratory testing, he was started on prednisone and mycophenolate, with good response. These medications were slowly tapered over the next 2 years, using clinical signs to guide the taper. At that time, because of the adverse effects of mycophenolate, the treatment was changed to intravenous immunoglobulin monthly infusions. During the 4.5-year follow-up period after diagnosis, while the systemic medications were being tapered, the patient's oral and skin lesions were well controlled, other than minor transient flares. However, a painful, ulcerated lesion on the facial gingiva between #11 and #12 was nonresponsive, even with use of topical clobetasol in trays. This recalcitrant lesion was vaporized with CO2 laser (3–5.5 W, continuous mode) under local anesthesia. This procedure resulted in complete healing of the ulceration, with no recurrence at the most recent 9-month postoperative examination. Conclusions Adjunctive procedures that can facilitate a decrease in the cumulative dosages of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is a safe procedure with minimal morbidity and no long-term side effects and should be considered as an adjunctive treatment option for management of recalcitrant lesions in patients with oral PV. Pemphigus vulgaris (PV) is a potentially fatal autoimmune, vesiculobullous, mucocutaneous disease. Recalcitrant oral lesions of PV can result in significant oral discomfort and interfere with eating and oral hygiene. Increasing the dosage of systemic medications to control such lesions results in higher risk of side effects. Currently, there is 1 published report describing 2 patients with healing of oral recalcitrant lesions after carbon dioxide (CO2) laser vaporization. We describe here a case of a 51-year-old male patient diagnosed with PV through biopsy and direct immunofluorescence in 2013. At baseline, the patient had a history of premature ventricular contractions, allergy to penicillin, occasional alcohol intake, and no tobacco use. He was on analgesics for mouth pain. After further baseline laboratory testing, he was started on prednisone and mycophenolate, with good response. These medications were slowly tapered over the next 2 years, using clinical signs to guide the taper. At that time, because of the adverse effects of mycophenolate, the treatment was changed to intravenous immunoglobulin monthly infusions. During the 4.5-year follow-up period after diagnosis, while the systemic medications were being tapered, the patient's oral and skin lesions were well controlled, other than minor transient flares. However, a painful, ulcerated lesion on the facial gingiva between #11 and #12 was nonresponsive, even with use of topical clobetasol in trays. This recalcitrant lesion was vaporized with CO2 laser (3–5.5 W, continuous mode) under local anesthesia. This procedure resulted in complete healing of the ulceration, with no recurrence at the most recent 9-month postoperative examination. Adjunctive procedures that can facilitate a decrease in the cumulative dosages of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is a safe procedure with minimal morbidity and no long-term side effects and should be considered as an adjunctive treatment option for management of recalcitrant lesions in patients with oral PV.