Oral epithelial dysplasia (OED) is a histopathological diagnosis that is associated with an increased risk of oral cancer. The purpose of this study was to compare the clinical features and long-term outcome of OED between users and non-users of tobacco and alcohol. The hospital records of 456 patients diagnosed as having OED were reviewed. Two groups of patients were selected based upon tobacco and alcohol usage: 37 patients who had neither smoked tobacco nor drank alcohol and 419 patients who both smoked tobacco and drank alcohol. OED in non-users of tobacco and alcohol was uncommon, accounting for only 8.1% of all OED. There was a male to female ratio of 1:1 in the group. The tongue and buccal mucosa were the most commonly affected sites. An erythro-leukoplakic-type lesion with mild dysplasia was the common presenting feature. Mixed type lesions with severe dysplastic changes, particularly of the gingiva, may progress to malignancy. These findings support the notion that OED may also develop in persons who have never used tobacco or alcohol. Lesions more commonly occurred in women, especially in the tongue and buccal mucosa, and were mostly of the erythroplakic type. The presence of OED in patients who do not smoke tobacco or drink alcohol suggests that risk factors other than alcohol and tobacco may exist. (J Oral Sci 52, 13-21, 2010)