Background: Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage. Methods: We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using ≤2 antihypertensive medications). Participants were prospectively examined for plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, brain-type natriuretic peptide, atrial natriuretic peptide, and 24-hour urinary aldosterone (UAldo), cortisol, sodium, and potassium values while adhering to a routine diet. Results: Plasma aldosterone (P<.001), aldosterone to renin ratio (P<.001), 24-hour UAldo (P=.02), brain-type natriuretic peptide (P=.007), and atrial natriuretic peptide (P=.001) values were higher and plasma renin activity (P=.02) and serum potassium (P<.001) values were lower in patients with resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P=.003), aldosterone to renin ratio (P=.02), 24-hour UAldo (P<.001), and urinary cortisol (P<.001) values than women. In univariate linear regression analysis, body mass index (P=.01), serum potassium (P<.001), urinary cortisol (P<.001), urinary sodium (P=.02), and urinary potassium (P<.001) values were correlated with 24-hour UAldo levels. Serum potassium (P=.001), urinary potassium (P<.001), and urinary sodium (P=.03) levels were predictors of 24-hour UAldo levels in multivariate modeling. Conclusions: Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as corticotropin, may underlie the aldosterone excess in patients with resistant hypertension. ©2008 American Medical Association. All rights reserved.