Abstract: Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.