AbstractNon‐invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non‐invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min;p< 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat;p< 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt;p< 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min;p< 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min;p= 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts;p= 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg;p= 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min;p< 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL,p= 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat,p= 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r= 0.67,p< 0.001), and arteriovenous oxygen difference (r= 0.59,p= 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non‐invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy.