Background Large marathons frequently involve widespread road closures and infrastructure disruptions, which may create delays in emergency care for nonparticipants with acute medical conditions who live in proximity to marathon routes. Methods We analyzed Medicare data on hospitalizations for acute myocardial infarction or cardiac arrest among Medicare beneficiaries (≥65 years of age) in 11 U.S. cities that were hosting major marathons during the period from 2002 through 2012 and compared 30-day mortality among the beneficiaries who were hospitalized on the date of a marathon, those who were hospitalized on the same day of the week as the day of the marathon in the 5 weeks before or the 5 weeks after the marathon, and those who were hospitalized on the same day as the marathon but in surrounding ZIP Code areas unaffected by the marathon. We also analyzed data from a national registry of ambulance transports and investigated whether ambulance transports occurring before noon in marathon-affected areas (when road closures are likely) had longer scene-to-hospital transport times than on nonmarathon dates. We also compared transport times on marathon dates with those on nonmarathon dates in these same areas during evenings (when roads were reopened) and in areas unaffected by the marathon. Results The daily frequency of hospitalizations was similar on marathon and nonmarathon dates (mean number of hospitalizations per city, 10.6 and 10.5, respectively; P=0.71); the characteristics of the beneficiaries hospitalized on marathon and nonmarathon dates were also similar. Unadjusted 30-day mortality in marathon-affected areas on marathon dates was 28.2% (323 deaths in 1145 hospitalizations) as compared with 24.9% (2757 deaths in 11,074 hospitalizations) on nonmarathon dates (absolute risk difference, 3.3 percentage points; 95% confidence interval, 0.7 to 6.0; P=0.01; relative risk difference, 13.3%). This pattern persisted after adjustment for covariates and in an analysis that included beneficiaries who had five or more chronic medical conditions (a group that is unlikely to be hospitalized because of marathon participation). No significant differences were found with respect to where patients were hospitalized or the treatments they received in the hospital. Ambulance scene-to-hospital transport times for pickups before noon were 4.4 minutes longer on marathon dates than on nonmarathon dates (relative difference, 32.1%; P=0.005). No delays were found in evenings or in marathon-unaffected areas. Conclusions Medicare beneficiaries who were admitted to marathon-affected hospitals with acute myocardial infarction or cardiac arrest on marathon dates had longer ambulance transport times before noon (4.4 minutes longer) and higher 30-day mortality than beneficiaries who were hospitalized on nonmarathon dates. (Funded by the National Institutes of Health.).