AbstractBackgroundPrior studies on the association between asthma and cancer show inconsistent results. This study aimed to generate additional evidence on the association between asthma and cancer, both overall, and by cancer type, in the United States.MethodWe conducted a retrospective cohort study using 2012–2020 electronic health records and claims data in the OneFlorida+ clinical research network. Our study population included a cohort of adult patients with asthma (n= 90,021) and a matching cohort of adult patients without asthma (n= 270,063). We built Cox proportional hazards models to examine the association between asthma diagnosis and subsequent cancer risk.ResultsOur results showed that asthma patients were more likely to develop cancer compared to patients without asthma in multivariable analysis (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.29–1.44). Elevated cancer risk was observed in asthma patients without (HR = 1.60; 99% CI: 1.50–1.71) or with (HR = 1.11; 99% CI: 1.03–1.21) inhaled steroid use. However, in analyses of specific cancer types, cancer risk was elevated for nine of 13 cancers in asthma patients without inhaled steroid use but only for two of 13 cancers in asthma patients with inhaled steroid use, suggesting a protective effect of inhaled steroid use on cancer.ConclusionThis is the first study to report a positive association between asthma and overall cancer risk in the US population. More in‐depth studies using real‐word data are needed to further explore the causal mechanisms of asthma on cancer risk.