The objective of this study was to establish whether ambulatory blood pressure offers a better estimate of cardiovascular risk than does its clinical blood pressure counterpart in refractory hypertension. This prospective study assessed the incidence of cardiovascular events over time during an average follow-up of 49 months (range, 6 to 96). Patients were referred to specialized hypertension clinics (86 essential hypertension patients who had diastolic blood pressure >100 mm Hg during antihypertensive treatment that included three or more antihypertensive drugs, one being a diuretic). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at the time of entrance. End-organ damage was monitored yearly, and the incidence of cardiovascular events was recorded. Patients were divided into tertiles of average diastolic blood pressure during activity according to the ABPM, with the lowest tertile <88 mm Hg (LT, n=29), the middle tertile 88 to 97 mm Hg (MT, n=29), and the highest tertile >97 mm Hg (HT, n=28). While significant differences in systolic and diastolic ambulatory blood pressures were observed among groups, no differences were observed at either the beginning or at the time of the last evaluation for office blood pressure. During the last evaluation, a progression in the end-organ damage score was observed for the HT group but not for the two other groups. Twenty-one of the patients had a new cardiovascular event; the incidence of events was significantly lower for the LT group (2.2 per 100 patient-years) than it was for the MT group (9.5 per 100 patient-years) or for the HT group (13.6 per 100 patient-years). The probability of event-free survival was also significantly different when comparing the LT group with the other two groups (LT versus MT log-rank, P<.04; LT versus HT log-rank, P<.006). The HT group was an independent risk factor for the incidence of cardiovascular events (relative risk, 6.20; 95% confidence interval, 1.38 to 28.1, P<.02). Higher values of ambulatory blood pressure result in a worse prognosis in patients with refractory hypertension, supporting the recommendation that ABPM is useful in stratifying the cardiovascular risk in patients with refractory hypertension.