Dirksen served in the House until 1946 when he left due to a series of health problems.
In 1952, Dirksen was a supporter of the presidential candidacy of fellow Senator Robert A. Taft of Ohio, the longtime leader of Republican conservatives. Dirksen garnered attention at the convention when he gave a speech attacking New York Governor Thomas E. Dewey, a liberal Republican and the leading supporter of Taft's opponent for the Republican presidential nomination, General Dwight Eisenhower. During the speech Dirksen pointed at Dewey on the convention floor and shouted "Don't take us down the path to defeat again", a reference to Dewey's presidential defeats in 1944 and 1948. His speech was met by cheers from conservative delegates and loud boos from pro-Eisenhower delegates. Despite Dirksen's efforts, Eisenhower defeated Taft for the nomination; Dirksen then supported Eisenhower's presidential candidacy.
In 1959, he was elected Minority Leader of the Senate, defeating Kentucky's more liberal Senator, John Sherman Cooper, by a vote of 20 to 14. Dirksen successfully united the various factions of the Republican Party by granting younger Republicans more representation in the Senate leadership and better committee appointments. He held the position of Senate Minority Leader until his death following cancer surgery on September 7, 1969 at Walter Reed Hospital in Washington, DC. Along with Charles Halleck and later Gerald Ford (the Republican Minority Leaders of the House), Dirksen was the official voice of the Republican Party during most of the 1960s, and he was often featured on television news programs. On several occasions during this period, political cartoonist Herblock depicted Dirksen and Halleck as vaudeville song-and-dance men, wearing identical elaborate costumes and performing an act called "The Ev and Charlie Show".
Dirksen's voting record was consistently conservative on economic issues. He developed a good rapport with the Senate's majority leaders, Lyndon B. Johnson and Mike Mansfield. On foreign policy, he reversed his early isolationism to support the internationalism of Republican President Dwight D. Eisenhower and Democratic President John F. Kennedy. He was a leading "hawk" on the issue of the Vietnam War — a position he held well before Democratic President Lyndon B. Johnson decided to escalate the war. Dirsken said in February 1964: [Dietz p 59]
First I agree that obviously we cannot retreat from our position in Vietnam. I have been out there three times, once as something of an emissary for then President Eisenhower. I took a good look at it. It is a difficult situation, to say the least. But we are in to the tune of some $350 million. I think the last figure I have seen indicates that we have over 15,500 military out there, ostensibly as advisors and that sort of thing. We are not supposed to have combatant troops, even though we were not signatories to the treaty that was signed at Geneva when finally they got that whole business out of the fire. But we are going to have to muddle through for a while and see what we do. Even though it costs us $1.5 million a day.As President Johnson followed Dirksen's recommendations and escalated the war, Dirksen gave him strong public support, as well as strong support inside the Republican caucus, even as some Republicans advised him that it would be to the party's advantage to oppose Johnson. Ford commented, "I strongly felt that although I agreed with the goals of the Johnson administration in Vietnam, I vigorously criticized their prosecution of the war. Now, Dirksen never took that same hard-line position that I took." [Dietz 149]
On March 22, 1966, Dirksen introduced a Constitutional amendment that would permit public school administrators to provide for organized prayer by students. This amendment was seen by many to violate the principle of separation of church and state, and was defeated in the Senate with only 49 affirmative votes, falling short of the 67 votes required for a Constitutional amendment.
He is most often remembered for the quip attributed to him: "A billion here, a billion there, pretty soon, you're talking real money". He made similar remarks but probably not that exact one. Dirksen is also quoted as having said "The mind is no match with the heart in persuasion; constitutionality is no match with compassion." (See Everett Dirksen.)
Dirksen was also legendary for his fondness for the marigold. When political discussions became tense, Dirksen would lighten the atmosphere by taking up his perennial campaign to have the marigold named the national flower. Although he was ultimately unsuccessful in his campaign, in 1972 his hometown of Pekin started holding an annual Marigold Festival in his memory, and now calls itself the "Marigold Capital of the World".
He recorded four albums in his resonant bass speaking voice, one of which, Gallant Men, unexpectedly made it to #29 on the U.S. Billboard charts and won a Grammy Award for Best Documentary Recording in 1968. Dirksen made TV guest appearances such as What's My Line, The Hollywood Palace and The Red Skelton Show.
Dirksen made a cameo appearance, not identified by name but effectively portraying himself, in the 1969 film The Monitors, a weird low-budget science-fiction movie in which invading extraterrestrials assert political dominion over the human race, claiming to do so for humanity's benefit.
In 1972, one of the Senate's buildings was renamed the Dirksen Senate Office Building in his honor.
Dirksen's daughter, Joy, was the first wife of Senator Howard Baker of Tennessee.