Background: On the basis of experimental chamber studies, vacuum cleaners with double-thickness bags and integral high-efficiency particulate arrest (HEPA) air filters are claimed to reduce airborne allergen levels and are currently recommended to allergic patients. Objectives: The objective of this study was to investigate the effect of vacuum cleaning on personal inhaled cat allergen exposure in homes with cats. Methods: Five unused new vacuum cleaners were compared with an old non-HEPA filter vacuum cleaner. Each vacuum cleaner was tested in an experimental chamber and in 5 homes with cats. Inhaled cat allergen was measured by nasal air sampling. Results: New vacuum cleaners failed to leak any allergen in the experimental chamber. There was a significant increase in inhaled cat allergen during vacuum cleaning in homes (F = 48.39, df = 1.4, P = .002) with no difference between the old vacuum cleaner and the unused new vacuum cleaners (5-fold and 3-fold increase compared to baseline, respectively; F = 0.005, df = 1.4, P = .95). Conclusions: The use of new HEPA-filter vacuum cleaners increases inhaled cat allergen in homes with cats. The use of HEPA-filter modern vacuum cleaners to reduce pet allergen exposure in the homes of pet owners should not be justified merely on the basis of experimental chamber data.