The use of electronic data capture (EDC) to assess health-related quality of life (HRQOL) using validated questionnaires is increasing; however, it must be determined how data collected electronically correlate with the original mode of administration used in validation. Our objective was to compare paper and electronic administration of the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), Pediatric Asthma Quality of Life Questionnaire (PAQLQ(S)), and Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ). Using a crossover design, adults and children with asthma and caregivers of children with asthma were recruited from clinics. Subjects were asked to complete both forms of the appropriate HRQOL measures at enrollment and 24-48 hours later. In addition, 30 subjects from each group were asked to participate in a 1-week reproducibility assessment of the electronic versions of the three questionnaires. Psychometric properties were assessed for each of the EDC versions. Intraclass correlation coefficients (ICC) and Pearson correlations were calculated to compare EDC and paper versions. A total of 51 adults (mean age 37, 73% females), 52 children (mean age 13, 38% females), and 51 caregivers (mean age 43, 92% females) were evaluated. Internal consistency (Cronbach's alpha) for the overall score of each questionnaire was: 0.96 for the AQLQ(S) and the PAQLQ(S), and 0.92 for the PACQLQ. Overall ICCs comparing paper with EDC were: 0.96 for the AQLQ(S), 0.91 for the PAQLQ(S), and 0.82 for the PACQLQ. Pearson's correlations were identical. One-week reproducibility (ICC) of the EDC versions was: 0.88 for the AQLQ(S), 0.78 for the PAQLQ(S), and 0.85 for the PACQLQ. When asked which method subjects preferred, the electronic version was chosen by 69% of adults, 77% of children, and 73% of caregivers. Additionally, 14% of adults, 14% of children, and 18% of caregivers reported no difference in preference. As in previous studies comparing electronic with paper questionnaires, this study revealed statistical evidence to support the use of EDC of the AQLQ(S), PAQLQ(S), and PACQLQ for populations with asthma.