The aim of the present study was to understand the risk of injury in relation to fitness in a retrospective occupational cohort of firefighters in Tucson, Arizona, from 2005 to 2009. Annual medical evaluations and injury surveillance data were linked to compare levels of aerobic fitness in injured employees with those in noninjured employees. The individual outcomes evaluated included all injuries, exercise-related injuries, and sprains and strains. Time-to-event analyses were conducted to determine the association between levels of fitness and injury likelihood. Fitness, defined by relative aerobic capacity (Vo(2max)), was associated with injury risk. Persons in the lowest fitness level category (Vo(2max) 43 mL/kg/minute) were 2.2 times more likely (95 confidence interval: 1.72, 2.88) to sustain injury than were those in the highest fitness level category (Vo(2max) 48 mL/kg/minute). Those with a Vo(2max) between 43 and 48 mL/kg/minute were 1.38 times (95 confidence interval: 1.06, 1.78) more likely to incur injury. Hazard ratios were found to be greater for sprains and strains. Our results suggest that improving relative aerobic capacity by 1 metabolic equivalent of task (approximately 3.5 mL/kg/minute) reduces the risk of any injury by 14. These findings illustrate the importance of fitness in reducing the risk of injury in physically demanding occupations, such as the fire service, and support the need to provide dedicated resources for structured fitness programming and the promotion of injury prevention strategies to people in those fields.