While cyclöoxygenase-2 inhibitors appear to be safe, hypertensive persons who use rofecoxib may experience increases in systolic blood pressure (SBP). In a randomized clinical trial involving hypertensive osteoarthritic subjects, use of rofecoxib 25 mg was associated with a 3 mm Hg increase in systolic blood pressure versus celecoxib 200 mg. Increased SBP among users of rofecoxib may be associated with increased risk of cardiovascular disease. OBJECTIVE: To estimate excess coronary heart disease (CHD) and stroke morbidity and mortality associated with a 3 mm Hg increase in SBP among U.S. adults with hypertension and osteoarthritis. METHODS: We used cardiovascular risk prediction models from the Framingham Heart Study and risk factor data from the Third National Health and Nutrition Examination Survey to estimate occurrences of CHD and stroke over four years among osteoarthritic persons with hypertension. We then estimated the effect of a 3 mm Hg increase in SBP on event occurrence and costs of cardiovascular disease treatment. RESULTS: An estimated 10.2 million U.S. osteoarthritics aged 35+ years are hypertensive. Among such persons, a 3 mm Hg increase in SBP may be associated with 20,800 additional CHD events (22% fatal) and 21,600 additional stroke events (26% fatal) over four years. The total cost of treating these events over four years is estimated to exceed US$650 million in year 2000 constant dollars. CONCLUSION: Increases in SBP associated with use of rofecoxib versus celecoxib may translate into significant cardiovascular morbidity and mortality and impose a sizable economic burden.