Respiration changes intrathoracic pressure and lung volumes in a cyclic manner, which affect cardiac function. Invasive ventricular pressure-volume (PV) loops can be recorded during ongoing mechanical ventilation or in transient apnea. No consensus exists considering ventilatory mode during PV loop recording. The objective of this study was to investigate the magnitude of any systematic difference of bi-ventricular PV loop variables recorded during mechanical ventilation versus apnea. PV loops were recorded simultaneously from the right ventricle and left ventricle in a closed chest porcine model during mechanical ventilation and in transient apnea (n=72). Variables were compared by regression analyses. Mechanical ventilation versus apnea affected regression coefficients for important PV variables including right ventricular stroke volume (1.22, 95% CI [1.08-1.36], p=0.003), right ventricular ejection fraction (0.90, 95% CI [0.81-1.00], p=0.043) and right ventricular arterial elastance (0.61, 95%CI [0.55-0.68], p<0.0001). Right ventricular pressures and volumes were parallelly shifted with Y-intercepts different from 0. Few left ventricular variables were affected, mainly first derivatives of pressure (dP/dt(max): 0.96, 95% CI [0.92-0.99], p=0.016, and dP/dt(min): 0.92, 95% CI [0.86-0.99], p=0.026), which might be due to decreased heart rate in apnea (Y-intercept -6.88, 95% CI [-12.22; -1.54], p=0.012). We conclude, that right ventricular stroke volume, ejection fraction and arterial elastance were mostly affected by apnea compared to mechanical ventilation. The results motivate future standardization of respiratory modality when measuring PV relationships.