Oral epithelial dysplasia (OED) is an important risk factor in predicting subsequent development of invasive carcinoma. Despite the malignant potential of OED, the current state of knowledge regarding aetiological risk factors associated with OED is limited. The aim of our study was to evaluate the aetiological role of alcohol consumption in non-tobacco smokers and smoking behaviour in non-drinkers, in patients presenting with OED. Data from a hospital-based case-control study of OED were used to analyse the risk associated with alcohol in non-smokers and with tobacco in non-drinkers. A total of 140 cases and 236 controls were included. In the non-drinkers, the risks of OED increased with tobacco smoking of more than 20 cigarettes per day, particularly non-filter cigarettes. The risk of OED declined following smoking cessation, with ex-smokers of 10 or more years demonstrating no excess risk relative to non-smokers. In the nonsmokers, consumption of alcohol was not a significant predictor of OED. However, there was a synergistic effect of alcohol when combined with some aspects of tobacco smoking. Our results confirm that tobacco has an independent role in the aetiology of OED. The role of alcohol, however, is principally only important in conjunction with tobacco use.