Factors underlying high healthcare utilization among Hispanic and African American (AA) children with asthma are not well known. We hypothesized that low parental knowledge and suboptimal practices are associated with high healthcare utlization and sought to elucidate these factors and identify ethnicity-specific differences. We also hypothesized that a targeted educational intervention will decrease emergency department (ED) visits and hospitalizations. A 57-item questionnaire investigating asthma knowledge, aptitude, and practice was administered during a hospitalization to 268 caregivers (158 Hispanic and 110 AA) of high healthcare utilizer children. Responses were compared between ethnicities. Participants were randomized into an education group and a control group to investigate the impact of an in-hospital educational intervention on future ED visits and hospitalizations. More than 80% of caregivers knew that asthma is associated with muscle constriction and mucus production. Overall, 66.7%-86.9% of caregivers found preventive steps including allergen avoidance, regular primary care physician (PCP) follow-up, and medication adherence helpful, but only 45.2% reported adherence to controller medications. Similarly, caregivers found management steps, including albuterol use, avoidance of ineffective medications, and need to contact PCP helpful but 33% Hispanic caregivers contacted their child's PCP at the time of the exacerbation leading the current hospitalization, compared with 17% AA caregivers (P=0.006). Moreover, 40% and 30% Hispanic and 27% and 18% AA caregivers felt stressed and helpless, respectively, about their child's asthma. Despite high baseline levels of knowledge, there were fewer ED visits in the education group (1.56±1.94) compared with the control group (2.05±2.32) (P=0.02) 2 years after the intervention. Although Hispanic and AA caregivers of children with high healthcare utilization were knowledgeable of asthma pathophysiology, and preventive and management steps, they reported being stressed and helpless and were unable to implement the steps at the time of an exacerbation, seeking care at the ED rather than contacting their PCP. The high health utilizers who underwent a targeted educational intervention had fewer ED visits 2 years following the intervention.