Background: There is no information about the clinical significance of the albuminbilirubin (ALBI) score in patients with hypertrophic cardiomyopathy (HCM). Objective:We retrospectively performed clinical evaluations in 462 patients with HCM to estimate whether the ALBI score could be a new tool to predict mortality in HCM. Methods and Results:During a median follow-up of 4.7 years, HCM-related death occurred in 52 (11.3%) patients. Overall, there was a significant positive association between ALBI score and HCM-related death (adjusted hazard ratio [HR]: 1.79 per one standard deviation [SD] increment, 95% confidence interval [CI]: 1.36-2.35). When the score was assessed as tertiles, the adjusted HRs of HCM-related death were 1.30 (95% CI: 0.42-3.99) for the tertile 2 and 4.43 (95% CI: 1.65-11.89) for the tertile 3, compared with the tertile 1. Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Meanwhile, time-dependent ROC analysis showed ALBI score could discriminate HCM-related death at various time points (AUC ranges: 0.725-0.850). Furthermore, exploratory analysis indicated the dynamic changes of ALBI score also could predict HCM-related death. Finally, multiple linear regression analysis suggested some pathogenetic pathways associated with HCM-related adverse outcomes significantly correlated with ALBI score, and the pathways included inflammation, myocardial injury, nutritional status and some clinical characteristics, but not abnormal cardiac structure and function itself. Conclusions:Higher ALBI score is a strong independent predictor of HCM-related death in patients with HCM. 2 Qiao et al.