Chronic respiratory diseases' (CRDs) impact on re-intubation rate remains unclear. We investigated the association between these factors in mechanically ventilated patients. Data were extracted from the freely available online Medical Information Mart for Intensive Care III database. CRDs were defined according to ICD-9 codes. Generalised linear regression and propensity score matching were performed. Of 13,132 patients, 7.9% required re-intubation. Patients with chronic obstructive pulmonary disease (COPD) had higher re-intubation (OR 2.48, 95% CI 1.83-3.33) and mortality rates (OR 1.64, 95% CI 1.15-2.34) than those without. Patients with asthma had a lower mortality rate (OR 0.63, 95% CI 0.43-0.92) but a similar re-intubation rate to those of patients without. These findings remained stable after propensity score matching and bootstrapping analysis. The association of COPD with re-intubation was significantly stronger in patients with high oxygen-partial pressure (PaO2) or mild disease severity but was independent of carbon dioxide partial pressure. Corticosteroid use was associated with increased re-intubation rates in subgroups without CRDs (OR 1.77-1.99, p < 0.001) but not in subgroups with CRDs. COPD patients with high post-extubation PaO2 or mild disease severity should be carefully monitored as they have higher re-intubation and mortality rates.