This study sought to develop a comprehensive measure of fitness that is predictive of injury risk and can be used in the fire service to assess individual-level health and fit-for-duty status. A retrospective occupational cohort of 799 career fire service employees was observed over the years 2005-2009. An equally weighted score for comprehensive fitness was calculated based on cardiovascular fitness, muscular strength, endurance, flexibility, and body composition. Repeated measures survival analyses were used to estimate the risk of any injury, sprain or strain, and exercise-related injuries in relation to comprehensive fitness. A well-distributed comprehensive fitness score was developed to distinguish three tiers of overall fitness status. Intraclass correlations identified flexibility, total grip strength, percent body fat, and resting heart rate as the most reliable fitness metrics, while push-ups, sit-ups, and aerobic capacity demonstrated poor reliability. In general, individuals with a lower comprehensive fitness status had an increased injury risk of injury as compared to the most fit individuals. The risk of any injury was 1.82 (95 % CI 1.06-3.11) times as likely for the least fit individuals, as compared to individuals in the top fire fitness category, increasing to 2.90 (95 % CI 1.48-5.66) when restricted to sprains and strains. This 5-year analysis of clinical occupational health assessments enabled the development of a relevant metric for relating comprehensive fitness with the risk of injury. Results were consistent with previous studies focused on cardiorespiratory fitness, but also less susceptible to inter-individual variability of discrete measurements.