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In 1828, Clay again supported Adams for President, and Jackson's success bitterly disappointed him. Although he intended to retire from politics, Clay was elected (1831) to the U.S. Senate and now led the National Republicans, who were beginning to call themselves Whigs (because they opposed Jackson's "tyranny"; see Whig party). Hoping to embarrass Jackson, Clay led the opposition in the Senate to the President's policies, but when the election came Jackson was overwhelmingly reelected.
Clay's chagrin was buried in the crisis developing over the tariff. South Carolina's nullification of the tariffs of 1828 and 1832 as well as Jackson's threats of armed invasion of that state allowed Clay to gain politically : working, even at the cost of his own protectionist views, toward a compromise with the John C. Calhoun faction, he helped to promote the Compromise Tariff of 1833.
Clay opposed the Jackson regime at every turn, particularly on the bank issue. When Jackson had the deposits removed (1833) from the Bank of the United States to his "pet banks," Clay secured in the Senate passage of a resolution : later expunged (Jan., 1837) from the record : censuring the President for his act.
Refusing to run for President in 1836, Clay continued his opposition tactics against Van Buren's administration and fought the subtreasury system in vain. In 1840, Clay lost the Whig nomination to William H. Harrison, mainly because of Thurlow Weed's adroit politics. Clay supported Harrison and, when Harrison was elected, was offered the post of Secretary of State, but he chose to stay in the Senate. He now planned to reestablish the Bank of the United States, but the unexpected accession of John Tyler to the presidency and his vetoes of Clay's bills caused Clay to resign his Senate seat.
In 1844 he ran against James K. Polk, an avowed expansionist. Earlier Clay had publicly opposed the annexation of Texas, and he restated his position in the "Alabama letters," agreeing to annexation if it could be accomplished with the common consent of the Union and without war. This maneuver probably lost him New York state, with which he could have won the election. His failure was crushing for him and for the Whig party. In 1848 his party refused him its nomination, feeling that he had no chance, and his presidential aspirations were never fulfilled.
He reentered (1849) the Senate when the country faced the slavery question in the territory newly acquired following the Mexican War. Clay denounced the extremists in both North and South, asserted the superior claims of the Union, and was chiefly instrumental in shaping the Compromise of 1850. It was the third time that he saved the Union in a crisis, and thus he has been called the Great Pacificator and the Great Compromiser.
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