ABSTRACT: Importance:Motor vehicle crashes (MVCs) are a leading public health concern. Emergency medical service (EMS) response time is a modifiable, system-level factor with the potential to influence trauma patient survival. The relationship between EMS response time and MVC mortality is unknown. Objectives:To measure the association between EMS response times and MVC mortality at the population level across US counties. Design, Setting, and Study Population:This population-based study included MVC-related deaths in 2268 US counties, representing an estimated population of 239 464 121 people, from January 1, 2013, through December 31, 2015. Data were analyzed from October 1, 2017, through April 30, 2018. Exposure:The median EMS response time to MVCs within each county (county response time), derived from data collected by the National Emergency Medical Service Information System. Main Outcomes and Measures:The county rate of MVC-related death, calculated using crash fatality data recorded in the Fatality Analysis Reporting System of the National Highway Traffic Safety Administration. Results:During the study period, 2 214 480 ambulance responses to MVCs were identified (median, 229 responses per county [interquartile range (IQR), 73-697 responses per county]) in 2268 US counties. The median county response time was 9 minutes (IQR, 7-11) minutes. Longer response times were significantly associated with higher rates of MVC mortality (≥12 vs <7 minutes; mortality rate ratio, 1.46; 95% CI, 1.32-1.61) after adjusting for measures of rurality, on-scene and transport times, access to trauma resources, and traffic safety laws. This finding was consistent in both rural/wilderness and urban/suburban settings, where a significant proportion of MVC fatalities (population attributable fraction: rural/wilderness, 9.9%; urban/suburban, 14.1%) were associated with prolonged response times (defined by the median value, ≥10 minutes and ≥7 minutes, respectively). Conclusions and Relevance:Among 2268 US counties, longer EMS response times were associated with higher rates of MVC mortality. A significant proportion of MVC-related deaths were associated with prolonged response times in both rural/wilderness and urban/suburban settings. These findings suggest that trauma system-level efforts to address regional disparities in MVC mortality should evaluate EMS response times as a potential contributor.