Abstract BACKGROUND We examined several novel biomarkers of different pathophysiologic pathways as predictors of cardiovascular mortality in participants enrolled in the Minnesota Heart Survey (MHS), a population-based study of cardiovascular disease (CVD) risk factors. METHODS In a nested case-control study within MHS, 7 biomarkers were assayed in serum samples from 211 patients identified after 8–15 years of follow-up who died of cardiovascular causes (cardiovascular heart disease, stroke, congestive heart failure) and 253 controls matched on age, sex, and study year. Logistic regression analysis, adjusted for age, race, sex, education, study year, smoking, abdominal obesity, diabetes, serum total cholesterol, systolic blood pressure, previous hospitalization for a CVD event, and other significant biomarkers, was used to evaluate the relations of biomarkers relative to the odds of CVD mortality. RESULTS Cases survived a median of 7.2 years after enrollment. Increased N-terminal pro-B type natriuretic peptide (NT-proBNP) (19% vs 4.3%), increased high-sensitivity C-reactive protein (hs-CRP) (71% vs 51%), and increased high-sensitivity cardiac troponin I (hs-cTnI) (8.7% vs 1.0%) were more common among cases than among controls (all P < 0.001 in unadjusted analyses). The adjusted odds of death were greater among cases compared to controls for increased NT-proBNP [odds ratio (OR) 5.67, 95% CI 2.17–15], hs-CRP (OR 1.73, 95% CI 1.03–2.89), and hs-cTnI (OR 8.53, 95% CI 1.68–43), and decreased ST2 (OR 1.92, 95% CI 1.05–3.48). CONCLUSIONS When measured by an hs-cTnI assay, cTnI is a key biomarker associated with increased cardiovascular death in a community sample when evaluated in a multiple biomarker analysis.