Background: Although frequent chronic obstructive pulmonary disease (COPD) exacerbation has been associated with the isolation of Pseudomonas aeruginosa (PA) in sputum cultures, it remains unknown whether the empirical use of anti-pseudomonal antibiotics can improve outcomes in patients with frequent COPD exacerbations. Research Question: Does empirical use of anti-pseudomonal antibiotics improve the length of the hospital stay in patients with recurrent COPD exacerbation?Study Design and Methods: This multicenter retrospective cohort study was conducted in seven hospitals in Japan. We included patients aged ≥40 years who were admitted to the hospital with COPD exacerbation more than twice during the study period (April 1, 2008 to July 31, 2020). The primary outcome was the length of the hospital stay. For statistical analysis, a log-linked Gamma model was used. Parameters were estimated using a generalized estimating equation model with an exchangeable correlation structure accounting for repeated observations from a single patient. Covariates included age, body mass index, home oxygen therapy use, respiratory rate, heart rate, oxygen use on admission, mental status, systemic steroid use, activities of daily living, and number of recurrences. Hospital-specific effects were specified as fixed effects.Results: Among 1573 patients with COPD exacerbation, 344 patients and 965 observations of recurrent COPD exacerbations were selected. Anti-pseudomonal antibiotics were used in 173 patients (18%). The estimated change in the length of the hospital stay between the anti-pseudomonal and non-anti-pseudomonal antibiotics groups was 0.044 days [95% confidence interval; -0.077, 0.166]. Interpretation: Use of empirical anti-pseudomonal antibiotics based only on recurrence may not be necessary. Further large-scale studies are needed to more precisely evaluate the effectiveness of empirical anti-pseudomonal antibiotics.