Treatment-related problems (TRPs) interfere with the ability to attain the desired goals of treatment, adding cost to healthcare systems. Patients hospitalized with acute conditions are at particular risk to experience TRPs. Data investigating such burden in patients with acute exacerbation of COPD (AECOPD) is generally scarce with no studies ever conducted in Jordan. This study aimed to investigate and categorize TRPs among patients hospitalized with AECOPD in Jordan, and to estimate their cost savings and cost avoidance. This was a retrospective population-based cohort study. Patients' cases of AECOPD admitted to the study site from Jan 2017 to Jul 2021 were identified from the electronic clinical database and screened for eligibility. TRPs were identified/categorized using AbuRuz tool and assessed for their severity. Cost saving was estimated by calculating all the extra costs. Cost avoidance was estimated according to Nesbit method. A total of 1243 (mean±SD 3.1±1.5) and 503 (mean±SD 1.3±1.2) TRPs were identified during hospitalization and at discharge respectively, of which 49.4% and 66.7% were classified as "unnecessary drug therapy". In 54.5% of the cases, systemic corticosteroid was administered for a period longer than recommended. Most of the TRPs were of moderate severity. The total direct cost saving, and cost avoidance were estimated to be 15,745.7 USD and 340,455.5 USD respectively. The prevalence and cost of TRPs among AECOPD patients is a concern requiring attention. The study results implicate integrating interventions such as embracing clinical pharmacists' role in the respiratory care units to optimize patients' management.