BACKGROUND AND PURPOSE: There is limited information regarding the cerebrovascular safety of cyclooxygenase 2 inhibitors (coxibs) and noncoxib nonsteroidal antiinflammatory drugs (NSAIDs). We determined whether specific NSAIDs, including coxibs, are associated with risk of stroke. METHODS: Retrospective cohort study among Tennessee Medicaid enrollees aged 50 to 84 years between January 1, 1999 and December 31, 2004. Noninstitutionalized persons with continuous enrollment in Medicaid and no stroke or other serious medical illness in the year before cohort entry were included. The 7 most common NSAIDs were examined: celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin. Nonuse of NSAIDs was the reference group. Because new use is less susceptible to bias, we conducted a similar analysis confined to new users. The outcome was hospitalization for an incident cerebrovascular event: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. RESULTS: The cohort included 336,906 persons, with 989,826 person-years of follow-up, and 4354 stroke hospitalizations. There were 4.51 strokes per 1000 person years in the nonuse group, 5.15 strokes per 1000 person years (adjusted HR 1.28, 95% CI 1.06, 1.53) with rofecoxib use, and 5.95 strokes per 1000 person years (adjusted HR 1.41, 95% CI 1.04, 1.91) with valdecoxib use. New use of rofecoxib and valdecoxib led to 6.06 (adjusted HR 1.46 95% CI 1.08, 1.98) and 6.19 (adjusted HR 1.39, 95% CI 0.74, 2.59) strokes per 1000 person years respectively. No other NSAID significantly increased the risk of incident stroke. CONCLUSIONS: Our results indicate an increased risk of stroke with current use of two highly selective coxibs, rofecoxib and valdecoxib, also shown to increase cardiovascular risk. These results also provide some reassurance about other specific NSAIDs regarding stroke risk.