OBJECTIVE: To investigate whether the alkylbisphosphonate etidronate is associated with an increased risk of gastrointestinal symptoms. METHODS: We conducted an observational follow-up study on a possible relationship between etidronate use and therisk of gastrointestinal symptoms in a cohort of 2754 women over 50 years of age. The study was performed with data on drug prescriptions obtained from the PHARMO database in the Netherlands. Women were included when they used either cyclical etidronate(n = 1050) or estrogen (n = 1704) for at least 14 days. They were followed-up for incident use of antiulcer drugs while on exposure medication. RESULTS: The mean ages were 72 years and 59 years in the etidronate and estrogen groups, respectively. In total, there were 95 women with incident prescriptions for gastrointestinal events after a median duration of follow-up of 2.7 months (range 0.1- 19.4 months). The crude relative risk of a gastrointestinal event for etidronate compared with estrogen use was1.2 [95% confidence interval (95% CI) 0.8-1.8]. Adjusted for baseline age, use of corticosteroids, salicylates and nonsteroidal anti-inflammatory drugs, the relative risk reversed to 0.6 (95% CI 0.4-1.2). CONCLUSION: The use of cyclical etidronate is notassociated with an elevated risk of symptoms of peptic ulcer disease.