BACKGROUND: The fibrosis-4 index (FIB-4) score, a noninvasive marker of subclinical liver fibrosis, has shown prognostic utility in general surgical populations. Current risk assessment models for patients with coronary artery disease undergoing percutaneous coronary intervention or coronary artery bypass grafting do not account for liver dysfunction apart from overt liver cirrhosis. We analyzed the distribution of the baseline FIB-4 score and its association with all-cause death in patients with coronary artery disease using data from the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial. METHODS: The baseline FIB-4 score was calculated for all ISCHEMIA randomized participants with laboratory data (platelet count, aspartate aminotransferase, and alanine aminotransferase). The primary outcome was the association between baseline FIB-4 and all-cause death. Secondary outcomes were cardiovascular death, heart failure, myocardial infarction, and stroke. Multivariable Cox regression was performed adjusting for key risk factors. RESULTS: The FIB-4 score was calculated for 3735 participants. Baseline FIB-4 score was significantly associated with an increased risk of all-cause (hazard ratio [HR], 1.19 [95% CI, 1.07-1.32]; P=0.001) and cardiovascular death (HR, 1.19 [95% CI, 1.04-1.36]; P=0.011). This association was consistent across the overall population and within subgroups of patients treated with percutaneous coronary intervention, coronary artery bypass grafting, and medical therapy. There was no significant association regarding heart failure, myocardial infarction, and stroke. CONCLUSIONS: The FIB-4 score may be a significant predictor of death in patients with coronary artery disease. Preprocedural hepatic assessment should be considered to stratify risk in patients undergoing invasive cardiac procedures.