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Treatment of cheilitis is usually difficult and often disappointing. We evaluated the effects of a topical preparation containing vitamin E acetate (VEA® lipogel) in 254 patients (mean age, 29.5) with cheilitis of various nature and etiology, involving the vermilion region and/or the perioral skin. The most frequent form of cheilitis was that induced by oral isotretinoin; other forms were irritant contact dermatitis, atopic cheilitis, and contact allergy. Patients were instructed to apply VEA® lipogel daily; the number of daily applications was modulated on the basis of the severity of symptoms (two or three times a day in the majority of cases). After 4 weeks of treatment, clinical examination showed that the severity of symptoms and signs significantly improved (P<0.001). The response to treatment was reported as particularly rapid by 32% of patients. Patient's assessment of overall effectiveness and acceptability was positive in the majority of cases. Treatment was well tolerated; local adverse reactions were observed in 2.75% of patients and were mostly transient and mild. Our experience suggests that VEA® lipogel is an effective and safe approach to cheilitis. The safety of this preparation is also due to the presence of only a few excipients and the absence of fragrances, preservatives and colouring agents.