OBJECTIVES: Antibiotics are often recommended as treatment for patients with COPD exacerbations. However, in many cases COPD exacerbations are not caused by a bacterial inflammation and antibiotics are prescribed unnecessary. Procalcitonin (PCT) is a biomarker with good specificity to distinguish bacterial from non-bacterial inflammations. It can prevent unnecessary antibiotic prescriptions and reduce duration of antibiotic therapy. The goal of this study is to compare the health and economic consequences of using a PCT-algorithm compared to current practice in hospitalized patients with COPD exacerbations. METHODS: A decision tree was developed, comparing the expected costs and effects of the PCT-algorithm to current practice in the UK, Germany and the Netherlands. The time horizon of the model captures the length of hospital stay and a societal perspective was adopted.  Model input data are based on a systematic literature research, country specific cost data sources and expert opinions. The primary health outcome was the duration of antibiotic therapy; the incremental cost-effectiveness ratio was defined as the incremental costs per antibiotic day avoided. RESULTS: Using a PCT-algorithm is expected to be cost-saving and more effective compared to current practice in all three countries. The incremental cost savings per antibiotic day avoided range from €125 in Germany and €90 in the Netherlands, to €52 in the UK. Probabilistic sensitivity analyses showed that the PCT-algorithm tends to dominate current practice, though decision uncertainty remains (Germany: 58%, UK: 57%, the Netherlands: 58%). Duration of hospital stay at baseline is the driver of the expected cost-savings in all three countries while reduction in antibiotic days drives the incremental effectiveness of the PCT-algorithm. CONCLUSIONS: A PCT-algorithm is a cost-effective way to guide the initiation and duration of antibiotic therapy when compared to current practice in COPD patients hospitalized with an exacerbation.