Systems and methods for determining cardiac output are disclosed. An illustrative method of determining cardiac output includes sensing an arterial pressure waveform using a pressure sensor located within a pulmonary artery, identifying a valve closure time associated with the pulmonary valve using the sensed arterial pressure waveform, estimating stroke volume using the systolic portion of the arterial pressure waveform and the valve closure time, and obtaining a measure of cardiac output based on the estimated stroke volume.