Despite increased 161-km ultramarathon participation in recent years, little is known about those who pursue such an activity. This study surveyed entrants in two of the largest 161-km trail ultramarathon runs in North America to explore demographic characteristics and issues that affected race performance. All entries of the 2009 Western States Endurance Run and the Vermont 100 Endurance Race were invited to complete a postrace questionnaire. There were 500 respondents among the 701 race entries (71.3% response). Finish time was found to have a significant (P ≤ .01) negative association with training volume and was generally directly associated with body mass index. Among nonfinishers, the primary reason for dropping out was nausea and/or vomiting (23.0%). Finishers compared with nonfinishers were more likely (P ≤ .02) to report blisters (40.1% vs 17.3%), muscle pain (36.5% vs 20.1%), and exhaustion (23.1% vs 13.7%) as adversely affecting race performance, but nausea and/or vomiting was similar between groups (36.8% vs 39.6%). Nausea and/or vomiting was no more common among those using nonsteroidal anti-inflammatory drugs (NSAIDs), those participating in the event with higher ambient temperatures, those with a lower training volume, or those with less experience at finishing 161-km races. Overall use of NSAIDs was high, and greater (P = .006) among finishers (60.5%) than nonfinishers (46.4%). From this study, we conclude that primary performance-limiting issues in 161-km ultramarathons include nausea and/or vomiting, blisters, and muscle pain, and there is a disturbingly high use of NSAIDs in these events.