Given the high mortality rate and the rapidly increasing incidence rate of esophageal carcinoma, chemopreventive agents are highly desirable. Aspirin has been shown to be associated with reduced risk of developing colorectal carcinoma and other cancers. Even though previous studies have shown reduced risk of esophageal cancer associated with aspirin use, results were inconsistent with respect to frequency and duration of use. In this hospital-based case-control study, 163 esophageal cancer cases were compared to 482 age- and sex-matched hospital controls with nonneoplastic conditions. Participants were classified as regular aspirin users if they had taken the drug at least once a week for 6 months. Results suggest that esophageal cancer risk is significantly lower for regular aspirin users compared to nonusers [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.86]. Individuals who used an equivalent of at least 1 aspirin a day (> or =7 tablets/week) were half as likely to have been diagnosed with esophageal carcinoma (aOR 0.47; 95% CI 0.26-0.85), and a linear trend was noted with increasing frequency of use (p(trend) 0.007). Similar protective effects were noted with < or =20 years of use, whereas no risk reduction was noted with >20 years of use. Consistent reduction in risk associated with aspirin use was noted among both the major histological subtypes, but the protective effect appears to be more pronounced in adenocarcinoma compared to squamous cell carcinoma. Overall, results from the current study suggest that regular aspirin use may be associated with reduced risk of esophageal cancer.