Abstract Background Whether heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of developing systolic dysfunction and a poor prognosis in hypertrophic cardiomyopathy (HCM) patients is unknown. Objective We aimed to assess risk factors for the development of end-stage (ES) heart failure (HF) (ejection fraction < 50%) and compare the prognosis of different HF phenotypes. Methods This retrospective study was conducted on patients with HCM in China between January 2009 and February 2023. Patients were stratified into three different groups: HCM-non-HF, HCM-HFpEF and HCM-heart failure with reduced ejection fraction (HCM-HFrEF). The primary outcome was a composite of major adverse cardiac events (MACEs), including all-cause deaths, HF hospitalization, sudden cardiac death and ventricular tachycardia. Results Of 3,620 HCM patients enrolled, 1,553 (42.9%) had non-HF, 1,666 (46.0%) had HFpEF, and 579 patients (11.1%) had HFrEF at baseline. During the median follow-up period of 4.0 years (IQR 1.4–9.4 years), patients with HCM-HFpEF exhibited a higher incidence of ES-HF than those with HCM-non-HF (12.4% vs. 2.7%, P < 0.001). HFpEF was an independent risk factor for ES-HF development (HR 3.84, 2.54–5.80, P < 0.001). MACEs occurred in 26.9% with a higher incidence in HCM-HFpEF than HCM-non-HF (36.6% vs 12.2%, P < 0.001). HFpEF was an independent predictor of MACEs (HR 2.13, 1.75–2.59, P < 0.001). Conclusions HFpEF is common in HCM. Compared to non-HF, it increases the risk of LVEF decline and poor prognosis. It may aid in risk stratification and need close echocardiography follow-up. Graphical Abstract Clinical Characteristics and Prognosis of Patients with Hypertrophic Cardiomyopathy and Heart Failure with Preserved Ejection Fraction. Abbreviations: ES-HF: end-stage heart failure; HCM: hypertrophic cardiomyopathy; HFpEF: heart failure with preserved ejection fraction; MACEs: major adverse clinical events