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Cardiac output (CO) is a major diagnostic and prognostic factor in pre-capillary pulmonary hypertension (PH). Reference methods for CO determination, like thermodilution (TD), require invasive procedures and allow only steady-state measurements. The Modelflow (MF) method is an appealing technique for this purpose as it allows non-invasive and beat-by-beat determination of CO.We aimed to compare CO values obtained simultaneously from non-invasive pulse wave analysis by MF (COMF) and by TD (COTD) to determine its precision and accuracy in pre-capillary PH. The study was performed on 50 patients with pulmonary arterial hypertension (PAH) or chronic thrombo-embolic PH (CTEPH). CO was determined at rest in all patients (n = 50) and during nitric oxide vasoreactivity test, fluid challenge or exercise (n = 48).Baseline COMF and COTD were 6.18 ± 1.95 and 5.46 ± 1.95 L·min-1, respectively. Accuracy and precision were 0.72 and 1.04 L·min-1, respectively. Limits of agreement (LoA) ranged from -1.32 to 2.76 L·min-1. Percentage error (PE) was ±35.7%. Overall sensitivity and specificity of COMF for directional change were 95.2% and 82.4%, (n = 48) and 93.3% and 100% for directional changes during exercise (n = 16), respectively. After application of a correction factor (1.17 ± 0.25), neither proportional nor fixed bias was found for subsequent CO determination (n = 48). Accuracy was -0.03 L·min-1 and precision 0.61 L·min-1. LoA ranged from -1.23 to 1.17 L·min-1 and PE was ±19.8%.After correction against a reference method, MF is precise and accurate enough to determine absolute values and beat-by-beat relative changes of CO in pre-capillary PH.