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Introduction: Pedestrian road safety remains a public health priority. The objective of this study is to describe trends in fatalities and injuries after pedestrian-motor vehicle collisions in the U.S. and identify associated risk factors for pedestrian fatalities., Methods: This is a cross-sectional study of U.S. pedestrian-motor vehicle collisions from 2006 to 2015 (performed in 2017). Pedestrian fatality and injury data were obtained from the National Highway Traffic Safety Administration's Fatality Analysis Reporting System and National Automotive Sampling System General Estimates System. Frequencies of fatalities, injuries, and associated characteristics were calculated. Multivariable logistic regression was performed for risk of fatality, controlling for demographic and crash-related factors., Results: There were 47,789 pedestrian fatalities and 674,414 injuries during the 10-year study period. Fatality rates were highest among the elderly aged 85 years and older (2.95/100,000 population), whereas injury rates were highest for those aged 15-19 years (35.23/100,000 population). Predictors associated with increased risk for death include the following: male sex (AOR=1.36, 95% CI=1.15, 1.62), age ≥65 years (AOR=3.44, 95% CI=2.62, 4.50), alcohol involvement (AOR=2.63, 95% CI=1.88, 3.67), collisions after midnight (AOR=5.21, 95% CI=3.20, 8.49), at non-intersections (AOR=2.76, 95% CI=2.21, 3.45), and involving trucks (AOR=2.15, 95% CI=1.16, 3.97) and buses (AOR=5.82, 95% CI=3.67, 9.21)., Conclusions: Potentially modifiable factors are associated with increased risk of death after pedestrian-motor vehicle collisions. Interventions including elder-friendly intersections and increasing visibility of pedestrians may aid in decreasing pedestrian injuries and deaths., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)