Abstract: Casualty estimation tools are critical in planning for nuclear event scenarios. Current consequence assessment models based on healthy adult males may not adequately represent the population. To develop an understanding of the impact of demographic variables on casualty estimates, human data was surveyed to identify key demographic factors that affect acute radiation response. Information on in utero exposures, gender, age, and comorbidity status was collected from atomic bomb survivors, radiation accidents, and clinical oncology. Burn and trauma studies were also examined to gain insight into the impact of demographic variables on acute injury outcomes. Fetal radiation sensitivity is well documented; increased mortality or malformations are observed depending on gestational age. A greater incidence of radiation syndrome was observed among male atomic bomb survivors. Trauma data show increased mortality in males, apparently due to immunological differences between genders. Limited data suggest vulnerability in the very young and old due to immunological status and comorbidities, respectively. Certain genetically susceptible subpopulations demonstrate marked increased sensitivity to radiation exposure. Interaction of radiation and comorbid conditions has not been well studied; however, burn and trauma data indicate that comorbidities negatively impact response to acute injury. Key factors evaluated together with their prevalence indicate the importance of modeling demographic variability in casualty estimations. Also they can help identify vulnerable subpopulations and provide insight on treatment requirements.