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Our study examines the association of the presence of mildew, cockroaches, and pets in homes as well as household dust allergens with the prevalence and/or severity of allergic diseases. No study has concurrently assessed home environment exposures in relation to allergic conditions in the general US population. Data from 5409 participants from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) living in their current homes for ≥one year were analyzed. Multivariate logistic regression analyses between home exposures and allergic diseases prevalence and severity were performed. In adjusted analyses, mildew was associated with higher current asthma, allergies, and allergic rhinitis prevalence; endotoxin, with higher current asthma prevalence; and dust Canis familiaris (Can f) 1, with higher allergic rhinitis prevalence. However, presence of cockroaches and dust Dermatophagoides farinae (Der f) 1 were associated, respectively, with lower current asthma and allergies prevalence. Presence of mildew, dust Der f1, Dermatophagoides pteronyssinus (Der p) 1, Felis domesticus (Fel d) 1, and endotoxin were all associated with asthma and/or wheeze severity. Non-atopic asthma was more frequent with mildew and/or musty smell dust and higher dust Fel d1 concentration, while atopic asthma was more prevalent with higher Can f1 and endotoxin concentrations in dust. This study confirms previous relationships and reports novel associations, generating hypotheses for future research.