Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on >/=3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 42 (16) nmol/L. Treatment with vitamin D did not reduce 24-hour ambulatory blood pressure (adjusted treatment effects: systolic, +3 mm Hg; 95% confidence interval, -4 to +11; P=0.33; diastolic, -2 mm Hg; 95% confidence interval, -6 to +2; P=0.29); similar results were seen for office blood pressure. Left ventricular mass index was measured in a subgroup (n=25); no reduction was seen with vitamin D treatment (adjusted treatment effect, +4 g/m(2); 95% confidence interval, 0 to +7; P=0.04). There was no significant change in cholesterol or glucose levels. Thus, 6 months of intermittent, high-dose oral vitamin D3 did not reduce blood pressure or left ventricular mass in patients with resistant hypertension.