High concentration oxygen therapy in patients with hypercapnic chronic obstructive pulmonary disease (COPD) is associated with increased mortality. In COPD patients at risk of hypercapnia, guidelines recommend oxygen therapy titrated to achieve oxygen saturation 88-92%. We investigated the association between adherence to guidelines and in-hospital adverse events.The study population comprised 117 patients (56% male, mean age 75 years) who experienced 161 admissions. Adverse events occurred in 39 (25%) of 157 admissions with data, comprising 12 deaths (6 had new acidosis), 16 new-onset acidosis episodes and 11 respiratory-related MET responses. Over-oxygenation occurred in 86% of admissions. The oxygen target was specified for 82% of admissions. Without oxygen target specification, 11/29 (38%) had adverse outcomes compared to 22% when specified. Duration of exposure to over-oxygenation was associated with adverse outcomes (p=0.001). Compared to the reference category (<24hrs), exposure for ≥4 days markedly increased odds of an adverse outcome (OR: 8.9; 95%CI: 2.6-30.5) after adjusting for age and Charlson comorbidity index. Adherence to guideline oxygen therapy in COPD inpatients is suboptimal. Over-oxygenation is common and is independently associated with in-hospital adverse events. This study reinforces the critical importance of accurate titrated oxygen delivery in hypercapnic COPD inpatients.