Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm  Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8  mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6  mm  Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6  mm  Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5  mm  Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5  mm  Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.