To assess the association of overall and specific mold levels in homes of urban children and difficult-to-control asthma.The study included 265 children from the Asthma Phenotypes in the Inner-City (APIC) study, aged 6 to 17 years old with asthma, and living in 8 urban cities across the United States. The study used 265 frozen-dust samples previously collected from the homes of APIC study-enrolled participants for analysis of mold concentrations. Although a total of 465 samples were collected during the APIC study, only the 265 samples that remained were used for post hoc analysis.The study was a cross-sectional analysis of 2 asthma cohorts: children with either difficult-to-control (DTC) and easy-to-control (ETC) asthma. DTC asthma participants required daily therapy of greater than or equal to 500 mcg fluticasone (with or without a long-acting β-agonist), and ETC asthma participants required less than or equal to 100 mcg fluticasone. Quantitative polymerase chain reaction assays were performed on frozen-dust samples that were obtained by wiping above-floor surfaces in participants’ homes using a Swiffer cloth (Procter and Gamble, Cincinnati, Ohio). The Environmental Relative Moldiness Index (ERMI) metric was used to classify mold species into 2 groups: group 1 (26 molds indicative of water damage in the home) and group 2 (10 molds commonly found indoors, even in homes without water damage). Average ERMI values and average concentrations of each of the 36 molds were compared in homes of children with DTC versus ETC asthma.No significant differences were found in average ERMI or average mold concentrations between homes of children with DTC asthma and ETC asthma. Mucor was the only mold with significantly greater average concentration in homes of children with DTC versus ETC asthma (average of 295 vs 67 cell equivalents per mg dust, P < .001). In homes with window air-conditioning (AC) units, the study found that Mucor concentration increased the probability of having DTC asthma (22% increase; 1.6 odds ratio) compared with ETC asthma.This study found that Mucor concentration is a predictor of DTC asthma, and homes with window AC units were more likely to have higher Mucor levels.Previous studies have shown an association between mold exposures and asthma. This study found that Mucor exposure in urban homes is associated with DTC asthma in a pediatric cohort with high geographic representation. Additionally, the study showed the association between elevated Mucor concentration, window AC units in urban homes, and the probability of DTC asthma. Further studies are needed to assess the role of decreasing home Mucor levels in reducing DTC asthma.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.jaci.2021.07.047