Among the most promising tests for early detection of congestive heart failure (CHF) are brain natriuretic peptides (BNPs), but it is unclear if homocysteine can aid in differentiating those with and without disease. We attempt to use a combination of tests to reduce the need for echocardiography without missing any cases of CHF. We compared 50 CHF patients with an ejection fraction of less than 60%, to 100 patients with non-specific symptoms but with a normal echocardiogram. After setting sensitivity at 100%, specificities for BNP, amino-terminal probrain natriuretic peptide (NT-pro BNP), and homocysteine were 34%, 28% and 36% respectively. Combinations of two tests if homocysteine was included increased the specificity to 56%. The AUC for BNP and NT-proBNP were not significantly different (92.8 and 95.9, respectively) whereas the AUC for BNP and NT-proBNP tests were superior to homocysteine (83.2). Compared with performing echocardiography in all patients, savings were dependent on the pretest probability. At a 1% pretest probability of CHF, savings were 44.5% while using a combination of NT-proBNP with homocysteine test. Homocysteine can be used in combination with either of the BNPs to decrease costs of early detection of CHF.