Low-cost air monitoring sensors are an appealing tool for assessing pollutants in environmental studies. Portable low-cost sensors hold promise to expand temporal and spatial coverage of air quality information. However, researchers have reported challenges in these sensors′ operational quality. We evaluated the performance characteristics of two widely used sensors, the Plantower PMS A003 and Shinyei PPD42NS, for measuring fine particulate matter compared to reference methods, and developed regional calibration models for the Los Angeles, Chicago, New York, Baltimore, Minneapolis-St. Paul, Winston-Salem and Seattle metropolitan areas. Duplicate Plantower PMS A003 sensors demonstrated a high level of precision (averaged Pearson′s r = 0.99), and compared with regulatory instruments, showed good accuracy (cross-validated R2 = 0.96, RMSE = 1.15 µg/m3 for daily averaged PM2.5 estimates in the Seattle region). Shinyei PPD42NS sensor results had lower precision (Pearson′s r = 0.84) and accuracy (cross-validated R2 = 0.40, RMSE = 4.49 µg/m3). Region-specific Plantower PMS A003 models, calibrated with regulatory instruments and adjusted for temperature and relative humidity, demonstrated acceptable performance metrics for daily average measurements in the other six regions (R2 = 0.74–0.95, RMSE = 2.46–0.84 µg/m3). Applying the Seattle model to the other regions resulted in decreased performance (R2 = 0.67–0.84, RMSE = 3.41–1.67 µg/m3), likely due to differences in meteorological conditions and particle sources. We describean approach to metropolitan region-specific calibration models for low-cost sensors that can be used with cautionfor exposure measurement in epidemiological studies.