Laryngeal leukoplakia can be a premalignant precursor of squamous cell carcinoma, is often tobacco-related and can usually be readily monitored by indirect laryngoscopy. One of the main motivations for using retinyl palmitate in patients with persistent leukoplakia was to avoid general anesthesia for elderly patients, who are considered to be high-risk patients when direct larynoscopy is required for possible tissue biopsy. Our study was the first to investigate the effectiveness and toxicity of high-dose retinyl palmitate in the treatment of laryngeal leukoplakia. Treatment was divided into two phases. In the first phase, all patients underwent induction therapy with 300,000 IU/day of retinyl palmitate for the 1st week, which was then adjusted up to 1,500,000 IU/day in the 5th week in patients with resistant lesions. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were assigned to a maintenance therapy of 150,000 IU/day. Complete remission was observed in 15 of 20 patients (75% of cases). Partial response was seen in the remaining 5 patients, with 3 of the patients relapsing. The median duration of treatment and follow-up was 18 months (range, 12-24 months). These results indicate that retinyl palmitate has substantial activity in laryngeal leukoplakias. Since only minor side effects were seen, the medication is an excellent candidate as a preventive agent for laryngeal cancer.