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The American Civil War (1861-1865). In it's most heated year the Civil War most likely cost over 300 fatalities per 100,000 citizens a year. This is not counting those who died from disease. Since it is also one of the only wars to have taken place on US soil, it can also be safely assumed to be the costliest in terms of monetary damage as well.

The next most deadly conflict was WW2 which cost the US about 10-140/per 100,000 citizens each year. In descending order, other costly conflicts were...

World War 1

American Revolution

War Of 1812

Korean Conflict

Vietnam War

http://www.violentdeathproject.com/

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Q: Most destructive war in us history?
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