Cardiac output (CO) is an important parameter for diagnosis and therapy of heart diseases, but it is still difficult to determine. Innocor, a novel noninvasive inert gas rebreathing (IGR) system, has shown promising results. However, the impact of pulmonary diseases on IGR remains unclear. The aim of the study therefore was to assess the accuracy and reliability of IGR in patients with distinct chronic lung disease. A total of 96 patients were enrolled, including 48 consecutive patients with variant lung diseases (group A) and 48 pair-matched pulmonary healthy patients (group B). CO was measured with cardiac magnetic resonance imaging (CMR) and IGR. Lung function testing was done by spirometry [FEV(1)/FVC (forced expiratory volume in one second/forced vital capacity), VC (vital capacity)] and determination of the diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA). In group A we found a mean CO of 4.7 ± 1.3 L/min by IGR and 4.9 ± 1.2 L/min by CMR. Group B showed a mean CO of 4.8 ± 1.4 L/min by IGR and 5.0 ± 1.3 L/min by CMR. Bland-Altman analysis revealed good correspondence between CMR and IGR, with an average deviation of 0.1 ± 1.0 L/min in group A and 0.1 ± 1.0 L/min in group B (p = 0.99). Multiple regression analysis for the pulmonary parameters did not show a statistically significant impact on the mean bias of CO measurements (FEV(1)/FVC: r = 0.01, p = 0.91; VC: r = -0.2, p = 0.13; and DLCO/VA: r = 0.04, p = 0.82). IGR allows a feasible determination of CO even in patients with lung diseases. The accuracy of the IGR method is not influenced by either pulmonary obstructive and restrictive diseases or a reduced DLCO.