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Background: To reduce antimicrobial resistance (AMR), initiatives such as surveillance activities and activities to increase knowledge about how and why antibiotics (ABs) are (mis)used are needed. More surveillance systems are in place in the WHO Western European region than in the Eastern region, and only sparse knowledge exists about the current culture of AB use in the Eastern European countries., Objective: To investigate AB knowledge, attitudes and behaviors in countries in the WHO Eastern European region in order to identify overall similarities and differences across the region and how AB knowledge, attitudes and behavior patterns may be influenced by the national health care system., Methods: Semi-structured interviews were conducted in Armenia, Georgia, Kazakhstan, Moldova, Russia and Tajikistan with patients, doctors and pharmacists. In total, 80 interviews were carried out. A directed content analysis was applied, followed by a comparative analysis, identifying the similarities and differences in AB attitudes, knowledge and behaviors between the countries and discussing how the national health care systems might influence these patterns., Results: Cross-national patterns were identified regarding patients seeking ABs over-the-counter (OTC), patient variations in their requests for ABs when consulting doctors, and, finally, doctors and pharmacists appearing knowledgeable about ABs and their uses, with doctors displaying careful attitudes towards AMR. Indications of national differences between the countries included the ability of patients to afford ABs, prescribing practices of doctors and pharmacist attitudes towards selling ABs without prescriptions. Multiple aspects involved in patient and pharmacist AB decision making were detected, such as various rationales involved in buying/selling ABs OTC, implying that these processes are more complex than previously reported in the literature., Conclusions: Similarities across the Eastern European region could be seen in patient needs and uses of antibiotics obtained OTC at community pharmacies, whereas doctors appeared more influenced by specific structures of the national healthcare system., (Copyright © 2019 Elsevier Inc. All rights reserved.)