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The comparison between Federal Equivalent Method (FEM) and Federal Reference Method (FRM) monitors in measuring fine particulate matter (PM2.5) concentrations frequently raises concerns about the accuracy and reliability of data. The comparability, or lack thereof, of data between FRM and FEM monitors may have significant implications for maintaining compliance with the National Ambient Air Quality Standards (NAAQSs). This study investigates the performance of continuous FEM monitors collocated with FRM monitors across 10 EPA regions in the U.S., focusing on PM2.5 measurements collected from 276 monitoring stations. Through an analysis of annually averaged paired concentration data, the study examines concentration ratios (FEM/FRM) and associated biases (in %, defined as [(FEM/FRM)−1] × 100) in FEM monitors across different manufacturers, measurement methods, EPA regions, and sampling location types. The study findings reveal a varied distribution of FEM/FRM ratios, with more than 50% of the FEM monitors having FEM/FRM > 1.1 and approximately 30% having FEM/FRM > 1.2. Substantial variations in estimated biases are identified among monitor types, measurement methods, EPA regions, and sampling site locations. Light scatter-based FEM monitors, notably Teledyne models 640 and 640x, dominate all locations (urban, suburban, and rural), with rural areas exhibiting higher mean bias values for both light scatter and beta attenuation FEM monitors (41% and 23%, respectively). On average, light scatter-based FEM monitors demonstrate higher biases compared to beta attenuation monitors across all EPA regions (28% vs. 12%). Irrespective of the measurement method employed, FEM monitors demonstrate a significant positive bias (mean bias 22%) relative to FRM monitors, which could result in an overestimation of PM2.5 design values (DVs) by 13–21% at monitoring sites designating FEMs as primary monitors for NAAQSs compliance designations. These findings emphasize the critical need to address method comparability issues, especially considering the recent tightening of NAAQSs for PM2.5 (annual) from 12 µg/m3 to 9 µg/m3 in the U.S. [ABSTRACT FROM AUTHOR]