Purpose: To correlate the severity of bronchiectasis in children with cystic fibrosis with clinical and microbiologic variables in order to clarify risk factors for the development of irreversible lung disease. Materials and Methods: After institutional review board approval and parental informed consents were obtained, a HIPAA-compliant longitudinal epidemiologic evaluation was performed in patients with cystic fibrosis who were enrolled in the Wisconsin trial of newborn screening from 1985 to 2009. Thinsection chest computed tomography (CT) was used in a prospective cross-sectional design to study patients ranging in age from 6.6 to 17.6 years (mean, 11.5 years). Thin-section CT scores were determined objectively on coded images by multiple raters in a standardized fashion. Microbiologic data were obtained by means of culture of respiratory secretions by using methods for differentiation of Pseudomonas aeruginosa (PA) as either nonmucoid or mucoid. Results: Eighty-three percent of patients (68 of 82) showed bronchiectasis of varying severity. Of 12 potential risk factors, only respiratory infection with mucoid PA correlated significantly with bronchiectasis (P = .041). Conclusion: The severity of bronchiectasis in children with cystic fibrosis is significantly related to respiratory infection with mucoid PA; attempts to prevent bronchiectasis should include reducing exposure to and early eradication of PA.