Vitamin D has been reported to lower blood pressure in vivo by regulating the renin-angiotensin system; however, there are limited clinical studies to support this finding in humans. We investigated the effect of vitamin D treatment on hypertension in a three-arm randomized placebo controlled pilot and feasibility study. We tested placebo with two forms of vitamin D: cholecalciferol (vitamin D3) and the active form of vitamin D, calcitriol. Subjects were recruited from the Atlanta Veterans Affairs Medical Center in Decatur, GA between April and August 2008. Subjects received 200,000IU of vitamin D3 (n=3) weekly for 3 weeks or matching placebo (n=3) weekly for 3 weeks (n=3) or 0.5μg calcitriol (n=2) taken twice daily for one week. Our primary endpoint was blood pressure measured by 24h ambulatory blood pressure monitor. Subjects receiving calcitriol experienced a 9% decrease in mean systolic blood pressure (SBP) compared placebo (p<0.001). One week after conclusion of calcitriol therapy SBP returned to pre-treatment levels. There was no reduction in blood pressure in the placebo or vitamin D3 groups. Results from this pilot study suggests that active vitamin D therapy may be an effective short-term intervention for reducing blood pressure and needs to be explored further in larger controlled studies. © 2010 Elsevier Ltd.