Elevated B-type natriuretic peptide (BNP) is a marker of poor outcomes in heart failure, acute coronary syndromes, and sepsis. Elevated cardiac troponin I (cTnI) is associated with adverse outcomes in infective endocarditis. It was hypothesized that elevated BNP would be associated with increased rates of morbidity and mortality in patients with infective endocarditis, particularly when combined with elevated cTnI. Consecutively enrolled patients in the International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) were evaluated at a single center. The association between elevated BNP and a composite outcome of death, intracardiac abscess, and central nervous system event and the individual components of the composite was determined. Similar analyses were performed in patients who had BNP and cTnI measured. Of 103 patients, 45 had BNP measured for clinical indications. The median BNP level was higher in patients with the composite outcome (1,498 vs 433 pg/ml, p = 0.03) and in those who died (2,150 vs 628 pg/ml, p = 0.04). Elevated BNP was significantly associated with the composite outcome (p <0.01) and intracardiac abscess (p = 0.02). Patients with elevation of BNP and cTnI had a significantly higher probability of the composite outcome (69%) than patients with either BNP or cTnI elevated (29%) or neither BNP nor troponin elevated (0%) (p for trend <0.01). In conclusion, these data demonstrate a significant association between elevated BNP alone and in combination with cTnI for serious outcomes in infective endocarditis and warrant prospective evaluation.