Abstract Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related somatic mutation associated with incident hematologic cancer. Environmental stressors which, like air pollution, generate oxidative stress at the cellular level, may induce somatic mutations and some mutations may provide a selection advantage for persistence and expansion of specific clones. Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) N = 4,379 and the Women's Health Initiative (WHI) N = 7,701 to estimate cross-sectional associations between annual average air pollution concentrations at participant address the year before blood draw using validated spatiotemporal models. We used covariate-adjusted logistic regression to estimate risk of CHIP per interquartile range increases in particulate matter (PM2.5; 4 μg/m3) and nitrogen dioxide (NO2; 10 ppb) as ORs (95% confidence intervals). Results: Prevalence of CHIP at blood draw (variant allele fraction > 2%) was 4.4% and 8.7% in MESA and WHI, respectively. The most common CHIP driver mutation was in DNMT3A. Neither pollutant was associated with CHIP: ORMESA PM2.5 = 1.00 (0.68–1.45), ORMESA NO2 = 1.05 (0.69–1.61), ORWHI PM2.5 = 0.97 (0.86–1.09), ORWHI NO2 = 0.98 (0.88–1.10); or with DNMT3A-driven CHIP. Conclusions: We did not find evidence that air pollution contributes to CHIP prevalence in two large observational cohorts. Impact: This is the first study to estimate associations between air pollution and CHIP.