BACKGROUND AND AIMS: The well-recognized gastrointestinal toxicity of NSAIDs ranges from mild symptoms to severe complications requiring medical attention and leading to work loss. The present study evaluates the economic burden derived from health care resource utilization and work loss caused by NSAID-induced gastrointestinal toxicity in the Swiss population. The costs induced by conventional and COX2-selective NSAIDs were calculated separately, and the results were then extrapolated for the United States. METHODS: A computer-generated random sampling of the Swiss population (n = 6,118) was administered a questionnaire by phone. Questions investigated NSAID intake, occurrence of adverse effects, consumption of gastroprotective drugs, health care resource utilization and work loss. Country-specific direct and indirect costs associated with NSAID-induced gastrointestinal toxicity were calculated according to current reimbursement costs in Switzerland and the United States. Medication expenses were used to compute separate iatrogenic cost factors for conventional and COX2-selective NSAIDs. The ability of demographic variables and symptoms to predict resource utilization was analyzed by univariate and multivariate analyses. RESULTS: From among the 6,085 responders (99.5% response rate), 294 subjects had gastrointestinal adverse effects associated with NSAID intake. The annual amount spent on NSAID-related adverse effects was CHF 432.2 million for Switzerland and USD 7,425.7 million for the United States. This amount corresponded to CHF 581 and USD 272 per NSAID user, and was primarily due to costs derived from work loss. For Switzerland, 91.1% of total costs were associated with the use of conventional NSAIDs and could be saved by using COX2-NSAIDs instead. While additional 13% of the medication purchase costs are spent for gastrointestinal adverse effects among COX2-selective NSAID users, additional 315% are spent for the same reason among conventional NSAID users. Thus, given similar efficacy and purchase costs in the two drug groups, COX2-selective NSAIDs are 25.1 times more cost-effective than conventional NSAIDs. Language region, place of residence, nationality, marital status, epigastric pain, diarrhea, hematemesis and melena predicted resource utilization. CONCLUSIONS: Costs arising from NSAID-induced gastrointestinal toxicity are considerable and primarily associated with conventional NSAIDs. COX2-selective NSAIDs could decrease this economic burden.