Background: Pseudomonas aeruginosa isolation in bronchiectasis is associated with a poor prognosis, including increased hospital admissions, exacerbation, and mortality. In this study, we aimed to evaluate the clinical characteristics and outcomes of P. aeruginosa isolation from patients with bronchiectasis in South Korea. Methods: This multicenter prospective cohort study analyzed 936 patients with bronchiectasis. We examined the prevalence of P. aeruginosa isolates and other microbiological characteristics. Additionally, the clinical characteristics related to disease severity and 1-year prognosis were compared between patients with and without P. aeruginosa isolation. Propensity score matching was used to mitigate confounding biases. Results: Of the 936 patients with bronchiectasis, P. aeruginosa was isolated from 89. A total of 445 matched patients—356 patients without (non-Pseudomonas group) and 89 with (Pseudomonas group) P. aeruginosa isolation—were analyzed. The Pseudomonas group showed poorer lung function, greater involvement of radiographic bronchiectasis, and a higher proportion of cystic bronchiectasis than the non-Pseudomonas group. After one year, more patients in the Pseudomonas group were admitted for bronchiectasis than in the non-Pseudomonas group. Moreover, the Bronchiectasis Health Questionnaire scores were significantly lower in the Pseudomonas group than in the non-Pseudomonas group. Conclusions: The isolation of P. aeruginosa was independently associated with increased disease severity and poor clinical outcomes in Korean patients with bronchiectasis.