Abstract Objectives: The aim of this study was to determine the effects of escalation of respiratory support and prolonged postoperative invasive ventilation on patient–centered outcomes, and identify perioperative factors associated with these two respiratory complications. Design: A retrospective cohort analysis of cardiac surgical patients admitted to cardiothoracic intensive care unit (ICU) between August 2015 and January 2018. Escalation of respiratory support was defined as ‘unplanned continuous positive airway pressure’, ‘non-invasive ventilation’ or ‘reintubation’ following surgery; prolonged invasive ventilation was defined as ‘invasive ventilation beyond the first 12 hours following surgery’. The primary endpoint was the composite of escalation of respiratory support and prolonged ventilation. Setting: Tertiary cardiothoracic ICU. Participants: A total of 2,098 patients were included and analyzed. Interventions: None. Measurements and Main Results: The composite of escalation of support or prolonged ventilation occurred in 509 patients (24.3%). Patients who met the composite had higher mortality (2.9% vs 0.1%; P<0.001) and longer median [interquartile range] length of ICU (2.1 [1.0–4.9] vs 0.9 [0.8–1.0] days; P<0.0001) and hospital (10.6 [8.0–16.0] vs 7.2 [6.2–10.0] days; P<0.0001) stay. Hypoxemia and anemia on admission to ICU were the only two factors independently associated with need for escalation of respiratory support or prolonged invasive ventilation. Conclusions: Escalation of respiratory support or prolonged invasive ventilation are frequently seen in cardiac surgery patients, and are highly associated with increased mortality and morbidity. Hypoxemia and anemia on admission to ICU are potentially modifiable factors associated with escalation of respiratory support or prolonged invasive ventilation.