Background While antibiotic therapy is advocated to improve outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) whenever mechanical ventilation is required, the evidence relies on small studies carried out before the era of widespread antibiotic resistance. Furthermore, the impact of systematic antibiotic therapy on successful weaning from mechanical ventilation was never investigated accounting for the competitive risk of death. The aim of the study was to assess whether early antibiotic therapy (eABT) increases successful mechanical ventilation weaning probability as compared to no eABT, in patients with AECOPD without pneumoniae, using multivariate competitive risk regression. Methods Retrospective analysis of patients admitted in 2 intensive care units (ICU) from 2012 to 2020 for AECOPD without pneumonia and requiring mechanical ventilation. eABT was defined as any anti-bacterial chemotherapy introduced during the first 24 h after ICU admission. The primary outcomes were the adjusted subdistribution hazard ratio (SHR) of the probability of being successfully weaned from mechanical ventilation (i.e. non-invasive and invasive ventilation) according to eABT status and accounting for the competitive risk of death. Results Three hundred and ninety-one patients were included, of whom 66% received eABT. eABT was associated with a lower probability of successful liberation from mechanical ventilation when accounting for the competing risk of death in multivariate analyses (SHR 0.71 [95% confidence interval, 0.57–0.89], p < 0.01), after adjustment with covariates of disease severity. This association was present in all subgroups except in patients under invasive mechanical ventilation on ICU day-1, in patients with ICU day-1 worst PaCO2 > 74 torr (median value) and in patients with a documented bacterial bronchitis at ICU admission. Ventilator-free days at day 28, ICU-free days at day 28 and invasive mechanical ventilation-free days at day 28, were significantly lower in the eABT group, while there was no significant difference in mortality at day 28 between patients who received eABT and those who did not. Conclusions eABT was independently associated with a lower probability of being successfully weaned from mechanical ventilation, suggesting that the clinician decision to overrule systematic administration of eABT was not associated with a detectable harm in AECOPD ICU patients without pneumonia.