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Background: Despite the high prevalence of co‐existing bronchiectasis and asthma (asthma‐bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. Objective: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. Methods: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady‐state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase‐chain‐reaction). Patients were followed‐up to record exacerbation and spirometry. Results: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria–virus co‐detection increased less substantially at acute exacerbations (AE) onset than at steady‐state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow‐up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate‐to‐severe bronchiectasis and non‐atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). Conclusion: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS. [ABSTRACT FROM AUTHOR]