IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension. No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people. OBJECTIVE To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension. DESIGN Parallel group, double-blind, placebo-controlled randomized trial. SETTING Primary care clinics and hospital clinics. PARTICIPANTS Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011. INTERVENTIONS A total of 100?000 U of oral cholecalciferol or matching placebo every 3 months for 1 year. MAIN OUTCOMES AND MEASURES Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months. RESULTS A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P?<?.001). No significant treatment effect was seen for mean (95% CI) office blood pressure (-1 [-6 to 4]/-2 [-4 to 1] mm Hg at 3 months and 1 [-2 to 4]/0 [-2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P?=?.24). CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN92186858.