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Yes there has. During Ulysses S. Grant's second term as the 18th President, his Vice President, Henry Wilson, died in office in 1875. He served for 2 years, 8 months.

William Rufus King, vice-president for Pierce died after about a month in office.

He was sick when he was sworn in and never actually got to Washington to serve.

Garrett Hobart, vice-president during McKinley's first term died in office. His death opened the way for Theodore Roosevelt to run with McKinley the second time.

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