: The clinical significance of () detection in the absence of allergic bronchopulmonary aspergillosis in cystic fibrosis (CF) airways remains unclear. Yet, some clinicians initiate antifungal therapy for positive respiratory cultures out of concern for infection in people with CF. : To determine the association between the presence of and respiratory outcomes in individuals with CF. : We conducted a prospective longitudinal cohort study of 206 adults and adolescents (age 14 and older) with CF and collected sputum for selective fungus culture. We assessed clinical outcome measurements, including patient reported outcomes (measured by the Cystic Fibrosis Questionnaire-Revised), spirometry, and number of pulmonary exacerbations (PEx) for a one-year period. We used mixed-effects linear models to determine the association between positive culture, defined as detection in sputum culture at the study visit, with both respiratory domain score and forced expiratory volume in one second (FEV) percent predicted, adjusted for confounders. Mixed-effects Poisson regression models were employed to examine the association between positive culture and PEx events. We explored the association between history, defined as detection at baseline or within two years of enrollment, and respiratory outcomes. : prevalence was 10.3% (95% CI 6.8,15.7) at baseline. Forty-eight (23.3%, 95% CI 17.7, 29.7) participants had at least one positive culture during the study period. Positive culture was not associated with a lower respiratory domain score. However, history was associated with a 6.48 point lower respiratory domain score, reflective of worse respiratory quality of life (95% CI -11.96, -0.99, p=0.02). Positive culture was associated with a 2.54% lower FEV percent predicted (95% CI -4.64, -0.44, p=0.02) and a 1.71-fold increase in severe PEx incidence (95% CI 1.05, 2.76, p=0.03). : Positive culture was not associated with lower patient-reported respiratory-related QOL. Yet, positive culture was associated with both lower FEV percent predicted and increased frequency of severe PEx warranting intravenous antibiotics in adolescents and adults with CF. Future studies are required to better understand the direct role of in lung disease progression in CF.