In a contemporary US population, one might expect transmission from introduced smallpox to be higher than we found to be typical. Population density is higher; mobility is greater, and, though more similar that one might think, immunity in the contemporary U.S. population is likely somewhat lower than in the populations studied. The healthcare workforce is also poorly vaccinated and inexperienced with smallpox. This will decrease the human resources available for care and containment, and increase the likelihood that initial cases will be missed. Counterbalancing this is the fact that few index cases will be vaccinated recently so the likelihood of more easily recognized typical cases is much higher. As the outbreak scenarios of greatest concern involve intentional release, outbreaks could be larger and more obvious than those reviewed, or could involve strains selected or engineered to be more virulent or contagious.