Background: Treatment with macrolide antibiotic clarithromycin in cardiovascular risk patients increases the risk of myocardial infarction and death from cardiovascular cause. Macrolides like clarithromycin, roxithromycin and especially azithromycin are frequently used worldwide for lower respiratory tract infections in COPD-patients.The objective of this study was to estimate the risk of cardiovascular events and  all-cause mortality among COPD-patients treated with these three macrolides. Treatment with amoxicillin was used as a reference. Methods: Nationwide cohort study among all severely ill COPD-patients treated in outpatient clinics in our country. The Danish health registers allowed for complete follow-up for all the defined outcomes in the 3-year follow-up period. We have divided out study population into four groups:amoxicillin, azithromycin, clarithromycin and roxithromycin. The main analysis was an adjusted cox proportional hazard model. As a sensitivity analysis, we used the inverse probability of treatment weighting method.Results: The primary outcome, which was major adverse cardiovascular events defined as stroke or acute myocardial infarction, we found no statistical differences between the groups in the adjusted cox proportional hazard regression analysis for the main COPD population (azithromycin: HR=1.01, CI95% 0.77-1.32, P value=0.96; clarithromycin: HR=0.92, 95%CI 0.65-1.32, Pvalue=0.66; roxithromycin:HR=0.91, CI95% 0.73-1.15, P value=0.45).The IPTW sensitivity analysis confirmed the findings in the main analysis.Conclusions:We found no differences between the antibiotics for MACE.