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Abstract Objective This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes. Research design and methods A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan–Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients. Results The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients. Conclusions The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis.