BACKGROUND Prehypertension (PreHT) and low-grade inflammation are both known to be related to the incidence of cardiovascular events. This cohort study investigated whether the high-risk group for future ischemic stroke among PreHT subjects can be predicted by stratification of high-sensitivity C-reactive protein (hsCRP). METHODS A total of 22,676 subjects aged 40-80 years from the general population who had no cardiovascular history underwent baseline measurement of serum hsCRP, and were followed for the incidence of ischemic stroke. RESULTS During the mean follow-up period of 2.7 years, 143 subjects had a first ischemic stroke. In a Cox multivariable model after adjustment for cardiovascular risk factors, there was no significant difference in hazard ratio (HR) for incidence of ischemic stroke between the normotension (NT) and PreHT subjects (HR = 1.72, 95% confidence interval (CI): 0.93-3.18, vs. NT subjects). In contrast, the HR for incidence of ischemic stroke in PreHT subjects with higher hsCRP levels (≥0.5 mg/l in men, ≥0.4 mg/l in women, more than median levels according to sex) was increased compared to NT subjects with lower hsCRP levels (HR = 2.63, 95% CI: 1.11-6.24). Moreover, the HR for incidence of ischemic stroke in PreHT subjects with lower CRP levels (HR = 0.91, 95% CI: 0.31-2.73) did not differ from that in NT subjects with lower hsCRP levels. CONCLUSIONS This study showed that, in a Japanese general population, hsCRP was a marker for relatively short-term risk of ischemic stroke in PreHT subjects.