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Background Left ventricular hypertrophy (LVH) is a risk marker for stroke and its regression confers protection from stroke. The relationship between serial LVH changes and risk of stroke has never been investigated in a mixed population of hypertensive subjects with and without LVH. Methods In this study, 880 initially untreated hypertensive subjects (mean age 48 years, office blood pressure (BP) 155/98 mm Hg; 24-h BP 137/87 mm Hg) underwent tests including echocardiography and 24-h ambulatory BP monitoring at entry and after a median of 3.5 years, still in the absence of cardiovascular events. Results Months or years after the follow-up study, 34 of these subjects developed a first cerebrovascular event (stroke in 21, transient ischemic attack in 13). Event rate (× 100 patients per year) was 0.25 among the subjects who never developed echocardiographic LVH or with regression of LVH, versus 1.16 among the subjects with lack of regression or new development of LVH (log-rank test: P = .00001). Serial electrocardiogram (ECG) changes failed to define groups at different risk. In a Cox analysis, the risk of cerebrovascular events was 2.8 times higher (95% CI: 1.18–6.69) in the subset with lack of regression or new development of LVH than in that with LVH regression or persistently normal LV mass. Such effect was independent of age (P = .001) and 24-h systolic BP (P = .003). Conclusions In a mixed hypertensive population with and without LVH at entry, serial changes in the echocardiographic indexes of LVH predict subsequent cerebrovascular events independently of office and ambulatory BP and other individual risk factors.