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Yellow Fever claimed the Majority of the US casualties.
It was brief, acconplished its mission, had limited casualties and many victorys.
about 650,000 total casualties
Secretary of State John Hay dubbed the Spanish-American War "a splendid little war" as the Spanish-American War is the shortest war in U.S. history with only 460 casualties. Also, the U.S. gained several territories which were then used for economical purposes: Guam, Cuba, Puerto Rico, and the Philippines.
tropical diseases
Mexico by a wide margin.
The Civil War
the most casualties in a war was the American Civil War with 495,332 deaths and behind it is WW2 with 405,399 deaths.
There was stiff and sometimes spirited resistence, but casualties were light on both sdes.
In Cuba
The U.S. Ambassador to Great Britain, John Hay, called the Spanish-American War a "splendid little war". The Spanish-American War, of course, resulted in mass casualties on both sides of the conflict.
The most important result of the Spanish-American War was the dissolution of the Spanish Empire. Peace was achieved by the signing of the Treaty of Paris on December 10, 1898.