Recent studies have demonstrated that high flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared to conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate post-operative period is less clear.Is routine HFNC use superior to COT or non-invasive ventilation (NIV) in preventing intubation in post-operative patients?and Methods: We comprehensively searched databases (MEDLINE, EMBASE, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use to COT or NIV in the immediate post-operative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay, post-operative hypoxemia and treatment complications. We assessed individual study risk of bias using the revised Cochrane ROB 2 tool and rated certainty in outcomes using GRADE framework.We included 11 RCTs enrolling 2201 patients. Ten compared HFNC to COT and one to NIV. Compared to COT, HFNC use in the post-operative period was associated with a lower reintubation rate (RR 0.32, 95% CI 0.12 to 0.88, 2.9% absolute risk reduction (ARR), moderate certainty) and decreased escalation of respiratory support (RR 0.54, 95% CI 0.31 to 0.94, ARR 5.8%, very low certainty). Post-hoc subgroup analysis suggested that this effect was driven by obese and/or high risk patients (subgroup differences, p 0.06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure or ICU LOS.With moderate certainty evidence, prophylactic HFNC reduces reintubation and escalation of respiratory support compared to COT in the immediate post-operative period following cardiothoracic surgery. This effect is likely driven by high risk and/or obese patients. These findings support post-op prophylactic HFNC use in the high risk/obese cardiothoracic patients.