The immediate transition from positive pressure mechanical ventilation to spontaneous ventilation may generate significant cardiopulmonary hemodynamic alterations based on the mode of weaning selected, particularly in individuals with preexisting cardiac dysfunction. The purpose of this study was to compare hemodynamic responses associated with the initial transition to 3 modes of ventilator weaning (spontaneous ventilation/T-piece, pressure support [PS], and continuous positive airway pressure [CPAP]). Right ventricular hemodynamic responses were evaluated with a thermodilution pulmonary artery catheter; while left ventricular hemodynamic responses were measured by a transducer-tipped Millar catheter and conductance catheter. Two groups of canines were studied. Group 1: normal biventricular function (n = 10) and group 2: propranolol-induced biventricular failure (n = 10). Dependent variables were measured at baseline on controlled mechanical ventilation (MV) and following the initial transition to each of 3 randomized spontaneous ventilatory conditions: T-piece, PS 5 cmH2O, and CPAP 5 cmH2O. Both groups significantly increased cardiac output in response to T-piece. Right ventricular stroke work was also significantly increased with T-piece and CPAP in both groups of subjects. Left ventricular response depended on baseline ventricular function. Baseline ventricular function influenced hemodynamic response to the immediate transition from mechanical to spontaneous ventilation. There were also differential hemodynamic responses based on the ventilatory mode. Consideration of baseline cardiac function may be an important factor in the selection of an appropriate mode of spontaneous ventilation following controlled MV.