Recommendation of the use of systemic steroids in chronic obstructive disease (COPD) exacerbation rely on trials that excluded patients requiring ventilatory support. In an open-label, randomised evaluation of oral prednisone administration, 217 patients with acute COPD exacerbation requiring ventilatory support were randomised (with stratification on the type of ventilation) to usual care (n=106) or to receive a daily dose of prednisone (1 mg·kg(-1)) for up to 10 days (n=111). There was no difference regarding the primary end-point, intensive care unit mortality, which was 17 (15.3%) deaths versus 15 (14%) deaths in the steroid-treated and control groups, respectively (relative risk 1.08, 95% CI 0.6-2.05). Analysis according to ventilation modalities showed similar mortality rates. Noninvasive ventilation failed in 15.7% and 12.7% (relative risk 1.25, 95% CI 0.56-2.8; p=0.59), respectively. Both study groups had similar median mechanical ventilation duration and intensive care unit length of stay, which were 6 (interquartile range 6-12) days versus 6 (3.8-12) days and 9 (6-14) days versus 8 (6-14) days, respectively. Hyperglycaemic episodes requiring initiation or alteration of current insulin doses occurred in 55 (49.5%) patients versus 35 (33%) patients in the prednisone and control groups, respectively (relative risk 1.5, 95% CI 1.08-2.08; p=0.015). Prednisone did not improve intensive care unit mortality or patient-centred outcomes in the selected subgroup of COPD patients with severe exacerbation but significantly increased the risk of hyperglycaemia.