The use of CO2 laser has become a routine procedure for the treatment of oral leukoplakia. In this retrospective study, we evaluated 65 patients with oral leukoplakia treated with CO2 laser vaporization. The main location was the tongue (n ¼ 21/65, 32.3%). The initial biopsy showed mild/moderate dysplasia in almost half the patients (n ¼ 29, 44.6%) and hyperplasia without dysplasia in around a third of the patients (n ¼ 21, 32.3%). The recurrence and malignant transformation rates were 33.8% (n ¼ 22) and 15.4% (n ¼ 10), respectively. The follow-up mean (standard deviation) was 15.0 (10.6) months. The procedure-related complications rate was 7.7% (n ¼ 5). The KaplaneMeier curves for time to recurrence showed differences only for gingiva lesions compared to tongue lesions (log rank, p ¼ 0.032). Malignant leukoplakia transformation is independent of treatment, although it seems advisable to treat leukoplakia with or without dysplasia.