AIMS: We aimed to characterize abnormal liver function tests in patients with heart failure (HF), as they are commonly encountered yet poorly defined. METHODS AND RESULTS: We used data from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) to characterize associations with baseline liver function tests (LFTs). Each LFT was analysed as both a continuous and dichotomous variable [normal vs. abnormal; bilirubin >1.0 mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >35 mmol/L]. Logistic regression assessed the association of LFTs and 30-day all-cause mortality and HF rehospitalization, and Cox proportional hazards assessed the association with 180-day all-cause mortality among patients alive at a 30-day landmark. In ASCEND-HF, 4228 (59%) had complete admission LFT data. Of these, 42% had abnormal bilirubin, 22% had abnormal ALT, and 30% had abnormal AST. Patients with abnormal LFTs were younger, had lower body mass index, and lower left ventricular ejection fraction. In multivariable models, increased total bilirubin was associated with increased 30-day mortality or HF rehospitalization [hazard ratio (HR) 1.17 per 1 mg/dL increase, 95% confidence interval (CI) 1.04, 1.32; P = 0.012], but not with an increase in 180-day mortality (HR 1.10, 95% CI 0.97, 1.25; P = 0.13) per 1 mg/dl increase. Compared with normal bilirubin levels, abnormal bilirubin was associated with increased 30-day mortality or HF rehospitalization (HR 1.24, 95% CI 1.00, 1.54; P = 0.048) and 180-day mortality (HR 1.32, 95% CI 1.08, 1.62; P = 0.007). We found no association with AST or ALT and outcomes. CONCLUSION: Greater than 40% of patients hospitalized with acute HF had abnormal LFTs. After multivariable adjustment, only elevated bilirubin was independently associated with worse clinical outcomes and may represent an important prognostic variable.