To evaluate the efficacy of school-supervised administration of once-daily inhaled corticosteroid to improve asthma control and reduce school absences in a primarily low-income Latino population.Students with asthma in 20 Tucson Unified School District elementary schools were selected to represent a large urban school population of low-income Latino students.The study was a 2-year, cluster-randomized, delayed-intervention trial comparing 9 months of supervised, unblinded, open-label mometasone furoate therapy with usual care. At entry, schools were randomized 1:1 to immediately initiate supervised therapy or delay implementation until year 2. Need for controller therapy was based on in-person evaluation the first year and by telemedicine during the second year. Medication was administered by school health personnel once daily on weekdays; parents were instructed to continue their own home medication during weekends and holidays. The primary outcome was change in Asthma Control Questionnaire (ACQ) score. Secondary outcomes included absences, unscheduled medical visits and hospitalizations, and oral steroid use.Nine hundred ninety-five (11%) of 8916 students reported asthma; 393 (39%) students enrolled, and 332 provided adequate data for analysis. Mean age was 8.1 years. At baseline, only one-fourth had well-controlled asthma. Thirty-nine percent reported controller medication use, and 80% were prescribed controller medication after clinical evaluation. During year 1, the mean ACQ score for students receiving immediate intervention did not significantly differ from those receiving delayed intervention. Medications were administered 98% of the time when students were at school; however, total calendar adherence was 53% due to absences, weekends, and holidays. Average school absences were noted to be 16 and 15 in immediate- and delayed-intervention groups, respectively, with only 4 to 5 of those due to asthma.School-supervised administration of once-daily inhaled corticosteroid did not result in improved asthma control as measured by ACQ, school absences, or health care use when compared with usual care in an urban, low-income, Latino elementary school population. Because of absences, weekends, and school holidays, the regimen achieved 53% calendar adherence despite excellent adherence to school-administered dosing. Further research is needed to clearly define the minimal adherence necessary to result in meaningful improvement in asthma control.There are numerous studies illustrating the benefits of school-supervised asthma therapy; this study provides a real-world application of school-based intervention with humbling but important results. Unique characteristics of the low-income Latino population and minimal research staff involvement may have played a role in outcomes and deserve further study. Of note is the high overall absenteeism rate and low calendar adherence rate. Hence, institution of school medication administration programs alone may not sufficiently impact asthma control without addressing home dosing and other societal determinants of school attendance and overall health.