Purpose Coagulation and inflammatory pathways are activated in heart failure (HF). This study attempts to address the utility of d-dimer as a biomarker of decompensated HF and compare its diagnostic accuracy with that of NTproBNP in the setting of activated neurohormonal pathways and pro-inflammatory molecules. Methods A retrospective crossectional/observational study was conducted in 162 patients with decompensated HF and 253 age-matched control subjects. All patients used in this study were ruled out for a pulmonary embolus by CT or VQ scans. Spearman's rank order correlation was performed between D dimer and NTproBNP. Level of significance was set at 0.05. Receiver-operating curves were constructed for D-Dimer and NTproBNP and a combination of both biomarkers to derive the area under the curve (AUC). Analyses were performed using SAS software. Study protocol was approved by TTUHSC IRB, Lubbock, TX. Results D-Dimer and NTproBNP showed a positive correlation (r=0.665, P=001). The AUC for NTproBNP= 0.963; for D-Dimer=0.928 and a combination of D-Dimer plus NTproBNP =0.982. The discriminatory power of D- Dimer was lower than that of NTproBNP. There is no difference in AUC values for D-dimer only versus D-Dimer and NTproBNP (p=0.21). The AUC for D-Dimer and NTproBNP combination is significantly better than using D-Dimer alone (p Conclusion D-dimer correlated significantly with NTproBNP in decompensated HF . Adding D-dimer to NTproBNP increased the area under the curve suggestive of increased diagnostic accuracy as a panel in acute decompensated HF. The discriminatory power of NTproBNP however remains better than that of d-dimer in this population.This is the first time a direct comparison of the diagnostic accuracy of D-dimer with NTproBNP has been made in the decompensated HFpopulation.