Self-efficacy is the personal belief that a behavior can produce a desired result; and in asthma, self-efficacy in asthma care has been related to improvements in asthma outcomes and children's quality of life. To appreciate the full burden of asthma on families, the relationship between parental self-efficacy and quality of life also needs further study. We aim to characterize this relationship. Secondary analysis of measurements of parents of children with persistent asthma ( = 252; ages 4-17 years) from a large urban area were identified from a randomized trial; the association between baseline assessments of parental quality of life, measured by the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), and parental self-efficacy, measured through the Parental Asthma Management Self-Efficacy Scale (PAMSES), were examined through multivariable linear regression. Parental self-efficacy in asthma was positively associated with quality of life among parents of racially and ethnically diverse children ( = 0.01). Confidence in using medications correctly ( = 0.03), having inhalers during a child's serious breathing problem ( = 0.02), and knowing which medications to use during a child's serious breathing problem ( = 0.04) were associated with a clinically meaningful difference in parental quality of life. Other significant factors associated with parental quality of life included Hispanic/Latino ethnicity ( < 0.01) of the child and Asthma Control Test scores ( < 0.01). The findings suggest that improving parental confidence on when and how to use their child's asthma medications, particularly during an asthma attack, might be clinically meaningful in enhancing parent's quality of life.