Although acute exacerbation of chronic obstructive pulmonary disease (AECOPD) will improve outcomes, the evidence for this belief comes mostly from small studies conducted before the age of widespread antibiotic resistance. In addition, the effect of systemic antibiotic medication on successful weaning off mechanical breathing has never been studied while taking the risk of death due to other causes into account. The purpose of this study was to use multivariate competitive risk regression to determine if early antibiotic therapy (eABT) in patients with AECOPD without pneumoniae increased the probability of effective mechanical ventilation weaning relative to no eABT. Analysis of patients hospitalized in ICUs between 2012 and 2020 with AECOPD who did not have pneumonia and who required mechanical ventilation. Any antibacterial chemotherapy started within the first 24 hours after ICU admission is considered early antimicrobial therapy (eABT). Success in weaning off mechanical ventilation (i.e., non-invasive and invasive ventilation) was the primary outcome, and the adjusted subdistribution hazard ratio (SHR) was calculated for each eABT status while taking into account the competing risk of mortality. In total, 391 patients were involved, with 66% receiving eABT. In multivariate studies (SHR 0.71 [95% confidence interval, 0.57–0.89], P<0.01), after controlling for confounding factors related to illness severity, eABT was associated with a reduced probability of achieving freedom from mechanical breathing. Excluding patients with proven bacterial bronchitis at ICU admission, patients on invasive mechanical ventilation on ICU day 1, and patients with a worse PaCO2 more than 74 torr (median value), this link was present in all subgroups. At day 28, there was no significant difference in mortality between the eABT and control groups, but the eABT group had considerably fewer ventilator-free days, fewer days in the intensive care unit, and fewer days in which invasive mechanical ventilation was required. There was no discernible injury in AECOPD ICU patients without pneumonia when clinicians decided to overrule the systemic administration of eABT, even though it was independently related to a reduced probability of being effectively weaned from mechanical ventilation.