Abstract There is still debate as to the safety of non-palliative opioid administration to chronic obstructive pulmonary disease (COPD) patients punctually treated for an acute complaint. All patients over 40 presenting at two university hospital emergency departments (Montréal Qc, Grenoble Fr) from March 2008 to September 2014 with dyspnea, abdominal pain or trauma were retrieved, and COPD patients were selected. Our primary endpoint was a composite criterion including invasive ventilation and death. Comparisons between visits in which opioid drugs were prescribed and those without opioids were performed using an inverse probability of treatment and censoring weight (IPTCW) estimator to adjust for baseline confounders. A survival weighted Cox model was used. 7799 visits by COPD patients were identified, corresponding to 4173 unique patients. Opioid drug prescription was reported in 1317 (16.9%) visits. After applying IPCTW weighting, opioid prescription was found to be associated with the composite criterion of poor clinical outcomes (HR = 4.73 (2.94; 7.61), p < 0.01). When taken separately, this association remained significant for invasive ventilation and death, but not for NIV. All sensitivity analyses confirmed the association, except for patients with trauma or abdominal pain as the main complaint. This excess risk is observed whatever the route of administration.