BackgroundApproximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD.MethodsIn a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004–2016 (n = 520), and estimated ambient PM2.5concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0–2 and 0–3 day lags of PM2.5concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5concentration at the median value.ResultsWe observed generally null or low-magnitude negative associations with short-term PM2.5exposure and respiratory-related (OR per 5 µg/m3increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5concentrations (OR per 5 µg/m3in 3-day lag PM2.5for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5concentrations (OR per 5 µg/m3in 3-day lag PM2.5for all-cause hospitalizations: 0.914 (0.804, 1.039)).ConcluisonsDifferences in associations demonstrate that people in areas with higher annual PM2.5exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5exposure.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12940-023-00999-4.