<p>Aspiration pneumonia (AP) is expected to have an increasing contribution to morbidity and mortality, particularly in the elderly population over the next coming decades. However, there are no reliable disease evaluation methods and prognostic indicators for patients with AP. A total of 841 patients with AP were included in this single-center prospective cohort study, among which 406 patients were in the eosinopenia group (an absolute eosinophil count &lt; 0.05 × 10⁹/L), and 435 patients were in the non-eosinopenia group (an absolute eosinophil count ≥ 0.05 × 10⁹/L). The primary outcome measure was 30-day overall mortality. The Cox proportional-hazards regression models with overlap weighting according to the propensity score were employed to estimate the associations between eosinopenia level and 30-day overall mortality. 841 AP patients (406 in eosinopenia, 435 in non-eosinopenia), mean ages (75.15 ± 16.76 years in eosinopenia, 78.23 ± 15.28 years in non-eosinopenia), 71 deaths within 30 days (62 in eosinopenia, 9 in non-eosinopenia), 30-day death rates were 15.27% in eosinopenia and 2.07% in non-eosinopenia), 30-day overall mortality hazard ratio by multivariate Cox regression (HR 3.884. for eosinopenia vs. non-eosinopenia, 95% CI 1.772–8.514), after propensity score weighting-overlap weighting (HR 2.337, 95% CI 1.052–5.194), sensitivity analyses ratio (HR 2.951, 95% CI 1.163–7.484) by propensity score matching and (HR 2.574, 95% CI 1.143–5.796) by propensity score regression. The Aspiration Pneumonia Patients with Low Eosinophil counts (APPLE) prospective cohort study suggested that eosinopenia in patients with AP was associated with an increased risk of 30-day overall mortality.</p><p>Trial registration: Chinese Clinical Trial Registry. URL <a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a>. Registration number ChiCTR2300076254. Registration date September 28, 2023.</p>