The Asthma Quality of Life Questionnaire for Native American Adults (AQLQ-NAA) was developed by modifying the Asthma Quality of Life Questionnaire-Marks (AQLQ-M) using the focus group technique. The 19-item AQLQ-NAA has emphasis on restrictions in social, community, and cultural activities. Higher scores indicate a better quality of life. The modified questionnaire was administered to a sample of 51 Native American adults with asthma at the Albuquerque USPHS Indian Hospital and its affiliated field clinics. Principal components analysis identified three domains with eigenvalues greater than 1.00: Community and Social Restrictions (CSR), Psychological Impact (PIM), and Symptoms (SYM). Cronbach's coefficient alpha for the AQLQ-NAA was 0.95 and ranged from 0.82 to 0.93 for the individual domains, indicating good internal consistency. The AQLQ-NAA score correlated negatively and significantly to urgent care visits, physician visits, and total number of medications taken for asthma in the past 6 and 12 months (p < 0.05). Additionally, the AQLQ-NAA score was correlated positively and significantly to medication adherence in the past 6 and 12 months (p < 0.05). Similar patterns of correlations were found with all three domain scores. These results indicated that there is evidence for the construct validity of the AQLQ-NAA and its domains. The AQLQ-NAA should provide a useful measure of HRQOL in asthma-specific medical interventions for the population in which it was developed.