Pseudomonas aeruginosa (PA) is commonly isolated from the respiratory secretions of antibody deficiency patients, but the significance of this has not been well studied. We have reviewed our adult antibody deficiency cohort of 179 patients and assessed the prevalence and characteristics of PA infection and the effects of early antibiotic eradication treatments. Of the 34 patients with PA, 55.9% (19) underwent successful eradication and were infection-free, 38.2% (13) had intermittent infection, and 5.9% (2) had chronic PA. PA infection was significantly associated with bronchiectasis (p < 0.0001), with 36.1% (22 out of 61) of patients with bronchiectasis developing a PA infection. Infection status was also significantly associated with chronic sinusitis (p < 0.0001). Most treated PA exacerbations were symptomatic and with colony counts of ≥1000 cfu/ml. Current eradication protocols used at our center involve early treatment at first positive isolate with ciprofloxacin for 3 weeks and nebulized colomycin for 3 months, and if eradication fails, intravenous ceftazidime and gentamycin or colomycin is administered for 2 weeks. Continued sputum surveillance and early eradication treatments upon positive PA culture may help to limit chronic PA infection in antibody deficiency patients.