U.S. officials began discussing the possibility of a regime change during the middle of 1963. The United States Department of State wanted to encourage a coup, while the Defense Department favored Diệm. Chief among the proposed changes was the removal of Diệm's younger brother Nhu, who controlled the secret police and special forces, and was seen as the man behind the Buddhist repression and more generally the architect of the Ngô family's rule. This proposal was conveyed to the U.S. embassy in Saigon in Cable 243.

The CIA contacted generals planning to remove Diệm and told them that the United States would not oppose such a move nor punish the generals by cutting off aid. On 1 November 1963, Ngô Đình Diệm was arrested and assassinated in a successful coup d'état led by General Dương Văn Minh. The U.S. ambassador to South Vietnam, Henry Cabot Lodge, invited the coup leaders to the embassy and congratulated them. Kennedy wrote Lodge a letter congratulating him for "a fine job". Kennedy dies the same month; Lyndon Johnson replaces him.