Aim: To evaluate the prognostic utility of red blood cell distribution width (RDW) and left ventricular mass index (LVMI) in patients with hypertrophic cardiomyopathy (HCM). Patients & methods: This study is a retrospective cohort analysis. Patients diagnosed with hypertrophic cardiomyopathy at the First Affiliated Hospital of Sun Yat-sen University from March 2014 to March 2019 were included . HCM patients were stratified into two groups based on the occurrence of major adverse cardiac events (MACE).Receiver operator characteristic (ROC) curves were then constructed and Cox regression models were employed to gauge the prognostic relevance of RDW and LVMI for HCM patients. Kaplan-Meier analysis evaluated the survival and MACE-free rate in patients with different level of RDW and LVMI. Results: A total of 300 patients with HCM were enrolled in this study and followed up for 40.56±18.33 months. Among them, 117 MACE (39.00%), 40 all-cause deaths (13.33%), 29 cardiovascular deaths (9.67%). The level of RDW, LVMI, creatinine (Cr) and B-type pro-brain natriuretic peptide (NT-ProBNP) were statistically different between the MACE group and Non-MACE group ( P<0.05). Multivariate analysis showed that after adjusting for confounding factors, RDW and LVMI were independent predictors of all-cause mortality and MACE in HCM patients. ROC showed that RDW>0.13 and LVMI>181g/m ² are the cut-off value to predict all-cause mortality and MACE. The AUC of the combination predicting the occurrence of all-cause mortality and MACE are 0.890 and 0.885 respectively. Kaplan-Meier analysis showed that the survival rate and MACE-free survival rate of group 1 (RDW≦0.13 and LVMI≦181g/m ²) were significantly higher than group 2 (RDW>0.13 or LVMI>181g/m ²), and group 3 (RDW >0.13 and LVMI>181g/m ²) ( P=0.000). Conclusion: We determined that increased RDW and LVMI was independently associated with MACE incidence and risk of mortality in HCM patients. Combined evaluation of RDW and LVMI yielded a more accurate predictive model of HCM patient outcomes relative to the use of either of these metrics in isolation. Our research can provide a theoretical basis in the occurrence of MACE for the high-risk HCM and intervene them properly and timely.