Blood eosinophil counts are used to inform diagnosis/management of eosinophilic asthma. Examine blood eosinophil variability and identify factors affecting eosinophil levels to inform clinical interpretation. analysis to understand eosinophil variability using data from four randomized controlled asthma trials. We examined ) influence of intrinsic/extrinsic factors (comorbidities, medication, and patient history) using baseline data ( = 2,612); ) monthly variation using placebo-treated patient data ( = 713); ) stability of eosinophil classification (<150, 150-299, and ⩾300 cells/μl) in placebo-treated patients with monthly measurements over a 1-year period ( = 751); and ) impact of technical factors (laboratory-to-laboratory differences and time from collection to analysis). Of intrinsic/extrinsic factors examined, nasal polyps increased eosinophil levels by 38%, whereas current smoking decreased levels by 23%. Substantial seasonal differences in eosinophil counts were observed, with differences of ∼20% between July and January. Eosinophil levels between 150 and 299 cells/μl were least stable, with 44% of patients remaining in the same classification for seven of 10 measurements versus 59% and 66% of patients in the <150 and ⩾300 cells/μl subgroups, respectively. Measurements at different laboratories showed high association (Spearman's correlation coefficient,  = 0.89); however, eosinophil counts were reduced, with longer time from collection to analysis, and variability increased with increasing eosinophil counts. Several intrinsic, extrinsic, and technical factors may influence, and should be considered in, clinical interpretation of eosinophil counts. Additionally, a single measurement may not be sufficient when using eosinophil counts for diagnosis/management of eosinophilic asthma.