Rationale: Pseudomonas aeruginosa is isolated from adults with chronic obstructive pulmonary disease (COPD) in cross sectional studies. However, patterns of carriage and the role of P. aeruginosa in COPD are unknown Objectives: To elucidate carriage patterns, phenotypes of strains, clinical manifestations and the antibody response to P. aeruginosa in COPD. Methods: A prospective study of adults with COPD was conducted. Isolates of P. aeruginosa were subjected to genotypic and phenotypic analysis. Sputum samples were studied for P. aeruginosa DNA and immune responses were assayed. Measurements: Analysis of longitudinal clinical data, sputum cultures, pulsed field gel electrophoresis of bacterial DNA, PCR of sputum, immunoblot assays of serum. Main Results: Fifty-seven episodes of acquisition of strains of P. aeruginosa were observed in 39 of 126 patients over 10 years. Acquisition of a new strain was associated with exacerbation. Thirty-one episodes of carriage were followed by clearance of the strain; 16 were of short (<1 month) duration. Thirteen strains demonstrated persistence and 13 were of indeterminate duration. Six strains were mucoid and were more likely to persist than nonmucoid strains (p=0.005). Antibody responses developed in 53.8% of persistent carriage and in only 9.7% of short term carriage episodes (p=0.003). Antibiotics did not account for clearance. Conclusions: Distinct patterns of carriage by P. aeruginosa were observed: 1) short term colonization followed by clearance and 2) long term persistence. Mucoid strains showed persistence. Acquisition of P. aeruginosa is associated with the occurrence of an exacerbation. Serum antibody responses do not mediate clearance of P. aeruginosa.