Blood pressure (BP) assessment may be vulnerable to bias by increased BP variability. Uncertainty in determining BP control is inherent to the clinic setting. We analyzed a registry of 3949 patients referred for ambulatory BP monitoring. The difference between clinic and ambulatory readings was plotted against ambulatory BP variability, assessed by standard deviation. In addition, BP variability of patients with clinic and awake ambulatory hypertension was compared with that of patients with controlled BP and sustained hypertension, respectively. The average clinic-ambulatory systolic BP difference was 5 ± 17/3 ± 9 mm Hg. Patients with >10-mm Hg systolic difference had higher systolic ambulatory BP standard deviation (14.9 ± 4.2 mm Hg) compared to patients with a difference of 0 to 10-mm Hg (standard deviation 12.5 ± 3.7 mm Hg). Patients with masking (negative clinic-ambulatory BP difference) also had comparatively higher standard deviation (14.4 ± 4.9 mm Hg P<0.0001). Greater ambulatory BP variability carried increased risk for both false diagnosis of hypertension (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.58-2.76), and missed clinic diagnosis of hypertension (OR: 1.86, 95% confidence interval: 1.48-2.33). The former was more striking in women, in whom high variability carried greater odds for false diagnosis of hypertension (OR: 2.76, 95% confidence interval: 1.96-3.89). Thus, clinic misjudgment of BP control may stem in part from high BP variability. Women with high BP variability are more susceptible to hypertension misdiagnosis. It is possible that high BP variability contributes to the increased cardiovascular risk related to both masked hypertension and white coat hypertension.