Background According to a recent meta-analysis, parathyroid hormone (PTH) excess is associated with increased cardiovascular disease (CVD) risk, but existing studies are limited. We examined in a prospective study the association of PTH with the incidence of CVD, taking into account vitamin D and other confounding variables. Methods The ARIC study measured PTH using a second-generation assay (Roche, Indianapolis, IN) in stored serum samples from 1990 to 1992 and related levels in 10,392 adults to incident cardiovascular outcomes (coronary heart disease [n = 808], heart failure [n = 1,294], stroke [n = 586], peripheral artery disease [n = 873], atrial fibrillation [n = 1,190], and CVD mortality [n = 647]) through 2010 (median follow-up 19 years). Results Contrary to the hypothesis, PTH level was not associated positively with any CVD outcome. The associations of incident heart failure, peripheral artery disease, and CVD mortality with PTH actually were weakly inverse (P trend = .02-.04) in the most fully adjusted models. For example, the hazard ratios across PTH quartiles were 1.00, 1.07, 1.07, and 0.96 (P trend = .74) for coronary heart disease incidence and were 1.00, 0.69, 0.74, and 0.74 (P trend = .02) for CVD mortality. Patterns were similar when restricted to participants with normal baseline kidney function. Conclusions This large prospective study failed to support the hypothesis that elevated PTH is an independent risk marker for incident CVD. When our data were added to the previous meta-analysis, the pooled hazard ratio remained statistically significant but weakened.