Background: Hypertrophic cardiomyopathy (HCM) patients are more susceptible to suffer from heart failure with normal ejection fraction (HFNEF). Therefore, it is critical to evaluate the relationship between left ventricular filling pressure (LVFP) and HFNEF, even if a large proportion of HCM patients have normal LVFP at rest. The objective was to assess the correlation between exercise tissue Doppler imaging (TDI) and early HFNEF in HCM patients by treadmill exercise echocardiography combined with cardiopulmonary exercise test (CPET). Method: Twenty-seven non-obstructive HCM patients and 31 age-and gender-matched healthy volunteers were enrolled in this study. All subjects underwent treadmill exercise echocardiography combined with CPET. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were analyzed before and after exercise. Result: Five HCM patients had normal LVFP at rest and increased after exercise. For this subgroup, the relationship between minute ventilation and carbon dioxide production (VE/VCO2 slope) and NT-proBNP levels were higher compared with controls and the subgroup with normal resting and stress LVFP, but was similar to the subgroup with elevated LVFP both at rest and after exercise. Conclusion: Elevated LVFP after exercise suggested the occurrence of early HFNEF in patients with non-obstructive HCM.