Adventure racing is a wilderness multisport endurance event with the potential for significant injury and illness; however specific contributing factors have not been extensively studied. A prospective cross-sectional study was conducted that collected data during the 2005 Adventure Racing World Championship on pre-, in- and post-race injury and illness and determined pre-race training volumes and health profiles in184 athletes (46 teams of 4 athletes). In the 6 months prior to the event, 79.9% of athletes reported an injury or illness. Fifty-nine cases of injury or illness were recorded during the race; representing an overall rate of 2.5 injuries per 1000 race-hours and 1.0 illness per 1000race-hours. This incidence could be considered low compared to some sports, but the rate is tempered by the time on course exposure of 16,774 race-hours. Respiratory conditions were the single-most common condition resulting in race withdrawal. There was a moderate, but not statistically significantly, association (OR = 4.61, p = 0.083, 95% CI 0.82–26.08) between pre-race illness and in-race illness. Forty-four (95%) teams responded to a post-race questionnaire with 30% of the athletes reporting a new injury and 12% reporting a new illness in the week following the race. Understanding contributing factors to injury and illness during adventure racing will aid implementation of race medical coverage, preventative strategies and increase participation and performance.