Treatment of oral leukoplakia has been disappointing with the available treatment modalities, because of inaccurate removal and an approximate 30% to 35% rate of recurrence. The CO2 laser has provided a promising new approach in the management of these lesions with very low morbidity and improved control. Twenty-nine patients were treated with the CO2 laser for 38 extensive (from 1 × 1 cm to 6 × 8 cm) intraoral leukoplakic lesions, 28 for cure and one for palliation. Microscopically the lesions varied from hyperkeratosis to carcinoma in situ. Follow-up of these patients ranges from 3 to 10 years, with an average of 5 years. An initial recurrence rate of 10.8% (4/37) was observed, and a 3-year local control rate of 97% after one to two procedures. A malignant transformation rate of 2.6% was encountered. Excellent wound healing and few complications were observed with this treatment approach. Surgical technique and results are reported supporting the advantages of the CO2 laser over conventional modes of treatment in the management of oral leukoplakia.