BACKGROUND How the prevalence of atrial fibrillation (AF) has changed over time in various demographic subgroups of patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT) in the United States is unknown. Whether in‐hospital outcomes differ between patients with AF versus patients without AF after MT remains uncertain. METHODS We conducted a serial cross‐sectional study using all primary AIS discharges in the 2010 to 2020 National Inpatient Sample. Discharges with MT codes were identified (n = 155 277), and the proportion with AF in various age, sex, and racial subgroups were computed. We used multivariable‐adjusted negative binomial regression to compare AF prevalence between demographic subgroups and joinpoint regression to evaluate trends over time. Multivariable‐adjusted generalized linear models were used to evaluate the association of AF with in‐hospital outcomes. RESULTS Across the study period, 45.0% of AIS discharges with MT had AF, but prevalence varied by age, sex, and race or ethnicity. After multivariable adjustment, AF prevalence was 4% higher in women versus men (prevalence rate ratio, 1.04 [95% CI, 1.01–1.07]) and was lower in Black versus White (prevalence rate ratio, 0.80 [95% CI, 0.77–0.84]) but higher in Asian compared with White discharges (prevalence rate ratio, 1.11 [95% CI, 1.05–1.18]). Prevalence increased with age (prevalence rate ratio for ≥80 years versus 18–39 years, 5.23 [95% CI, 4.28–6.39]). Following joinpoint regression, prevalence increased by 3.2% (95% CI, 1.3%–5.2%) annually across the period 2010 to 2015 but declined by −2.2% (95% CI −2.9% to −1.4%) from 2015 to 2020. AF was associated with 22% lower odds of in‐hospital death (odds ratio, 0.78 [95% CI, 0.71–0.85]) and 13% greater odds of routine home discharge (odds ratio, 1.13 95% CI, 1.04–1.22]) compared with no AF. CONCLUSION AF prevalence in patients undergoing MT in the United States is approximately twice that of the general AIS population. AF prevalence in MT increased from 2010 to 2015 but declined from 2015 to 2020. In the subset of patients with AIS undergoing MT, AF is associated with reduced in‐hospital death.