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Introduction: Chronic obstructive pulmonary disease (COPD) patients are at higher risk for pulmonary embolism (PE) due to limited mobility, smoking, inflammation or comorbidities. High D-dimer levels have been detected in many diseases including COPD exacerbation, even in the absence of detectable PE. Aims and Objectives: To determine the optimal D-dimer cutoff value for the diagnosis of PE, in patients hospitalized for COPD exacerbation. Methods: We retrospectively analyzed 180 consecutive patients, admitted to “KAA” and 5 th Respiratory Clinic of Athens Chest Hospital “Sotiria” for COPD exacerbation, according to Anthonisen criteria, during 2014. Fifty from the above patients were found to have been investigated with computed tomography angiography despite a low probability for PE (Wells score). All 50 patients had D-Dimer levels measured as well. Receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of D-dimer measurements in diagnosing PE. Results: Fifty patients (72.1±12.0 years old) were included in the analysis. PE was detected in 10 patients (20%). D-dimer levels of COPD patients with PE (median value: 7655 mcg/L) were significantly higher than those of the patients without PE (median value: 940 mcg/L)(p Conclusions: Patients hospitalized for COPD exacerbation with low clinical probability for PE present D-dimer levels higher than normal, even without PE. The D-dimer cutoff value used to exclude PE should be adjusted, thus reducing the unnecessary use of diagnostic procedures.