Respiratory weaning after cardiac surgery can be difficult or prolonged in up to 22.7% of patients. The inability to wean from a ventilator within the first 48 h after surgery is related to increased short- and long-term morbidity and mortality. Risk factors are mainly non-modifiable and include preoperative renal failure, New York Heart Association, and Canadian Cardiac Society classes as well as surgery and cardio-pulmonary bypass time. The positive effects of pressure ventilation on the cardiovascular system progressively fade during the progression of weaning, possibly leading to pulmonary oedema and failure of spontaneous breathing trials. To prevent this scenario, some parameters such as pulmonary artery occlusion pressure, echography-assessed diastolic function, brain-derived natriuretic peptide, and extravascular lung water can be monitored during weaning to early detect hemodynamic decompensation. Tracheostomy is considered for patients with difficult and prolonged weaning. In such cases, optimal patient selection, timing, and technique may be important to try to reduce morbidity and mortality in this high-risk population.