Regular exercise is associated with substantial health benefits; however, little is known about the health impact of extreme levels of exercise. This study examined the prevalence of chronic diseases, health-care utilization, and risk factors for exercise-related injuries among ultramarathon runners. Retrospective, self-reported enrollment data from an ongoing longitudinal observational study of 1,212 active ultramarathon runners were analyzed. The most prevalent chronic medical conditions were allergies/hay fever (25.1%) and exercise-induced asthma (13.0%), but there was a low prevalence of serious medical issues including cancers (4.5%), coronary artery disease (0.7%), seizure disorders (0.7%), diabetes (0.7%), and human immunodeficiency virus (HIV) infection (0.2%). In the year preceding enrollment, most (64.6%) reported an exercise-related injury that resulted in lost training days (median of 14 days), but little nonattendance of work or school due to illness, injury, or exercise-related medical conditions (medians of 0 days for each). The knee was the most common area of exercise-related injury. Prior year incidence of stress fractures was 5.5% with most (44.5%) involving the foot. Ultramarathon runners who sustained exercise-related injuries were younger (p<0.001) and less experienced (p<0.01) than those without injury. Stress fractures were more common (p<0.01) among women than men. We conclude that, compared with the general population, ultramarathon runners appear healthier and report fewer missed work or school days due to illness or injury. Ultramarathon runners have a higher prevalence of asthma and allergies than the general population, and the prevalence of serious medical issues was nontrivial and should be recognized by those providing medical care to these individuals. Ultramarathon runners, compared with shorter distance runners, have a similar annual incidence of exercise-related injuries but higher proportion of stress fractures involving the foot, and it is the younger and less experienced ultramarathoners who appear most at risk for injury.