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Background: Respiratory disease and, specifically, pneumonia, is the major cause of mortality and morbidity in young children. Diagnosis of both pneumonia and asthma in primary care rests principally on clinical signs, history taking, and bronchodilator responsiveness. This study aimed to describe clinical practices in diverse global primary care settings concerning differential diagnosis of respiratory disease in young children, especially between pneumonia and asthma. Methods: Health professionals in Greece, Kyrgyzstan, Vietnam, and Uganda were observed during consultations with children aged 2–59 months, presenting with cough and/or difficult breathing. Data were analyzed descriptively and included consultation duration, practices, diagnoses and availability/use of medications and equipment. The study is part of the European Horizon 2020 FRESH AIR project. Results: In total, 771 consultations by 127 health professionals at 74 facilities in the four countries were observed. Consultations were shorter in Vietnam and Uganda (3 to 4 minutes) compared to Greece and Kyrgyzstan (15 to 20 minutes). History taking was most comprehensive in Greece. Clinical examination was more comprehensive in Vietnam and Kyrgyzstan and less in Uganda. Viral upper respiratory tract infections were the most common diagnoses (41.7% to 67%). Pneumonia was diagnosed frequently in Uganda (16.3% of children), and rarely in other countries (0.8% to 2.9%). Asthma diagnosis was rare (0% to 2.8%). Antibiotics were prescribed frequently in all countries (32% to 69%). Short acting β-agonist trials were seldom available and used during consultations in Kyrgyzstan (0%) and Uganda (1.8%), and often in Greece (38.9%) and Vietnam (12.6%). Conclusions: Duration and comprehensiveness of clinical consultations observed in this study seemed insufficient to guide respiratory diagnosis in young children. Appropriate treatment options may further not be available in certain studied settings. Actions aiming at educating and raising professional awareness, along with developing easy-to-use tools to support diagnosis and a general strengthening of health systems are important goals. [ABSTRACT FROM AUTHOR]