In the face of a growing public health concern accompanying the reemerging threat of preventable diseases, this research seeks mainly to explain variations in the perceived benefits and risks of vaccinations among the general public in the United States. As Mary Douglas and Aaron Wildavsky's grid-group cultural theory of risk perception claims, the analytical results based upon original data from a nationwide Internet survey of 1,213 American adults conducted in 2010 suggest that individuals’ cultural predispositions contribute to the formation of their perceptions pertaining to vaccine benefits and risks at both societal and individual levels, in conjunction with other factors suggested by previous risk perception literature, such as perceived prevalence of diseases, trust, knowledge level, and demographic characteristics. Those with a strong hierarch orientation tend to envision greater benefits and lesser risks and conceive of a relatively high ratio of benefit to risk when compared to other cultural types. By contrast, those with a strong fatalist tendency are inclined to emphasize risks and downplay benefits while conceiving of a low vaccination benefit-risk ratio. Situated between hierarchs and fatalists, strong egalitarians are prone to perceive greater benefits, smaller risks, and a more positive benefit-risk ratio than strong individualists.