Objectives This study investigated whether lower 25-hydroxyvitamin D and higher parathyroid hormone concentrations are associated with incident hypertension. Background Disturbances in vitamin D metabolism are plausibly related to hypertension. Methods MESA (Multi-Ethnic Study of Atherosclerosis) is a community-based, prospective cohort with baseline measurements obtained between 2000 and 2002. We studied 3,002 men and women free of prevalent cardiovascular disease and hypertension, age 45 to 84 years at baseline. Serum 25-hydroxyvitamin D and intact parathyroid hormone were measured from previously frozen baseline samples using liquid chromatography-mass spectroscopy and a 2-site immunoassay, respectively. We used a complementary log-log model with interval censoring to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for 25-hydroxyvitamin D and parathyroid hormone concentrations with incident hypertension through 2010. Results During a median follow-up of 9.0 years, 41% of the cohort (n = 1,229) developed hypertension. Mean serum 25-hydroxyvitamin D was 26.3 ± 11.2 ng/ml and mean parathyroid hormone was 41.2 ± 17.3 pg/ml. Compared with 25-hydroxyvitamin D ≤30 ng/ml, 25-hydroxyvitamin D <20 ng/ml was associated with a greater hypertension risk (HR: 1.28 [95% CI: 1.09 to 1.50]), although the association was attenuated and not statistically significant after adjusting for potential confounders (HR: 1.13 [95% CI: 0.96 to 1.33]). Compared with parathyroid hormone <33 pg/ml, parathyroid hormone ≤65 pg/ml was associated with a significantly greater risk of hypertension (HR: 1.27 [95% CI: 1.01 to 1.59]) after adjusting for potential confounders. Conclusions Lower 25-hydroxyvitamin D concentrations were not associated with a greater risk of incident hypertension. Higher serum parathyroid hormone concentrations showed a significant, but statistically marginal, relationship to the development of hypertension. These findings will require further confirmation. (Multi-Ethnic Study of Atherosclerosis; NCT00005487). © 2014 by the American College of Cardiology Foundation.