The spectrum of injuries associated with femoral shaft fractures and those injuries' association with mortality have not been well delineated previously. Patients in the National Trauma Data Bank who presented with femoral shaft fractures from 2011 to 2012 were analyzed in 3 age groups (18-39, 40-64, and 65+ years). For each group, modified Charlson Comorbidity Index (CCI), mechanism of injury (MOI), injury severity score (ISS), and associated injuries were reported. Multivariate logistic regression was used to identify predictors of mortality. Among the 26,357 patients with femoral shaft fractures, modified CCIs gradually increased with increasing age category and ISS decreased. Motor vehicle accidents were the most common MOI in the younger 2 age groups, whereas falls were the most common MOI in the 65 years and older age group. The top 3 associated bony injuries for the study cohort as a whole were tibia/fibula (20.5%), ribs/sternum (19.1%), and non-shaft femur (18.9%, of which 5.8% of the total cohort were femoral neck) fractures. The top 3 associated internal organ injuries were lung (18.9%), intracranial (13.5%), and liver (6.2%), injuries. A multivariate mortality analysis showed that increasing age, increasing comorbidity burden, and associated injuries all had independent associations with mortality. The injuries most associated with mortality were thoracic organ injuries (adjusted odds ratio [AOR]=3.53), head injuries (AOR=2.93), abdominal organ injuries (AOR=2.78), and pelvic fractures (AOR=1.80). This study used a large, nationwide sample of trauma patients to profile injuries associated with femoral shaft fractures. Associations between injuries and mortality underscore the importance of these findings. [Orthopedics. 2017; 40(3):e506-e512.].