If the Vice-Presidency became vacant through death or resignation, the President would then nominate a new Vice President, who would take office upon confirmation by a majority vote in both the House and Senate.

Prior to 1967, when the Twenty-fifth Amendment was ratified, there was no procedure in place for filling a vacancy in the vice-presidency. The office was left vacant until the next election. That happened 16 times in U.S. history. The last instance was when Vice President Lyndon Johnson became President after John Kennedy's assassination in 1963.

Since its ratification in 1967, the Twenty-fifth Amendment process has been invoked twice: in 1973 President Richard Nixon nominated Gerald Ford to replace Spiro Agnew, who had resigned mid-term; and in 1974, when Gerald Ford became President after Richard Nixon's resignation. He named Nelson Rockefeller to be Vice-President. Gerald Ford thus holds the distinction in American history of serving as both Vice-President and President without having been elected to either office.