Background: The management of erectile dysfunction in men with hypertrophic cardiomyopathy remains controversial, since phosphodiesterase 5 inhibitors can theoretically increase left ventricular outflow tract pressure gradient (PG), yet this increase may not be detected at rest. Case Description: Two hemodynamic supine bike stress tests with transthoracic echocardiography were performed on two subsequent mornings in a 65-year-old man with hypertrophic cardiomyopathy and episodes of presyncope. The patient was instructed to take Tadalafil before the first stress test, and Tadalafil and Vardenafil before the second stress test. Results: The left ventricular outflow tract PG recorded by continuous-wave Doppler in the transapical view increased between rest and peak exercise: DPG on Tadalafil = +37 mmHg; DPG on Tadalafil and Vardenafil = +124 mmHg. Conclusion: This report demonstrates a novel use of serial provocation imaging studies aimed at comparing left ventricular PGs at peak stress during the initiation and dose titration of phosphodiesterase 5 inhibitors. Further studies are needed to develop an evidence-guided algorithm for safe implementation of therapies for erectile dysfunction in this most common inherited cardiomyopathy.