A prospective study included 50 patients (mean age 68 ± 12 years, 54% female) with suspected or confirmed pulmonary hypertension who underwent right heart catheterization. The hemodynamic effects of cycle ergometry (10–50 W) and low-intensity isometric handgrip exercise (20% of maximal force), each lasting 6–7 min in the semi-recumbent position, were compared. Both modalities caused significant changes in hemodynamic parameters compared to rest, but the changes at handgrip were significantly smaller. Mean pulmonary artery pressure increased by 14 mmHg with cycle ergometry versus 4 mmHg with handgrip (p < 0.001). Pulmonary artery wedge pressure (PAWP) increased by 5 mmHg versus 2 mmHg (p < 0.001) and cardiac output by 1.5 L/min versus 0.2 L/min. In patients with PAWP ≤ 15 mmHg at rest, there was an increase in PAWP of more than 25 mmHg in two cases with cycle ergometry, but in none with handgrip. Isometric handgrip exercise is not a suitable substitute for cycle ergometry in right heart catheterization.