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Background: Cough is symptomatic of a broad range of acute and chronic pediatric respiratory illnesses. No studies in children have tested for an extended panel of upper airway respiratory viruses and bacteria to identify whether they predict cough outcomes, irrespective of clinical diagnosis at the time of acute respiratory illness (ARI). We therefore determined whether upper airway microbes independently predicted hospitalization and persistent cough 28-days later in children presenting with an ARI, including cough as a symptom., Methods: A cohort study of children aged <15-years were followed for 28-days after presenting to a pediatric emergency department with an ARI where cough was also a symptom. Socio-demographic factors, presenting clinical features and a bilateral anterior nasal swab were collected at enrolment. Polymerase chain reaction assays tested for seven respiratory bacteria and 17 viruses. Predictors of hospitalization and persistent cough at day-28 were evaluated in logistic regression models., Results: Eight hundred and seventeen children were included in the analysis; median age 27.7-months. 116 (14.2%, 95%CI 11.8, 16.6) children were hospitalized and 163 (20.0%, 95%CI 17.2, 22.7) had persistent cough at day-28. Hospitalized children were more likely to have RSV A or B detected on nasal swab than those not admitted (adjusted relative risk (aRR) 1.8, 95%CI 1.0, 3.3). M. catarrhalis was the only microbial difference between children with and without cough persistence (aRR for those with cough at day 28: 2.1, 95%CI 1.3, 3.1)., Discussion: An etiologic role for M. catarrhalis in the pathogenesis of persistent cough post-ARI is worth exploring, especially given the burden of chronic cough in children and its relationship with chronic lung disease. Pediatr Pulmonol. 2017;52:373-381. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)