There has been increased interest in the prophylactic and therapeutic use of high-flow nasal oxygen in patients with, or at risk of, non-hypercapnic respiratory failure. There are no randomised trials examining the efficacy of high-flow nasal oxygen in high-risk cardiac surgical patients. We sought to determine whether routine administration of high-flow nasal oxygen, compared with standard oxygen therapy, leads to reduced hospital length of stay after cardiac surgery in patients with pre-existing respiratory disease at high risk for postoperative pulmonary complications. Adult patients with pre-existing respiratory disease undergoing elective cardiac surgery were randomly allocated to receive high-flow nasal oxygen (n = 51) or standard oxygen therapy (n = 49). The primary outcome was hospital length of stay and all analyses were carried out on an intention-to-treat basis. Median (IQR [range]) hospital length of stay was 7 (6-9 [4-30]) days in the high-flow nasal oxygen group and 9 (7-16 [4-120]) days in the standard oxygen group (p=0.012). Geometric mean hospital length of stay was 29% lower in the high-flow nasal group (95%CI 11-44%, p = 0.004). High-flow nasal oxygen was also associated with fewer intensive care unit re-admissions (1/49 vs. 7/45; p = 0.026). When compared with standard care, prophylactic postoperative high-flow nasal oxygen reduced hospital length of stay and intensive care unit re-admission. This is the first randomised controlled trial examining the effect of prophylactic high-flow nasal oxygen use on patient-centred outcomes in cardiac surgical patients at high risk for postoperative respiratory complications.