In 1991, Fidel Ramos resigned as Defense secretary to run for president. Aquino appointed de Villa as his replacement. When Ramos won as President in 1992, he reappointed de Villa to the post.
In 1997, he resigned as Defense secretary and made his bid for the presidency. He joined Lakas-NUCD the same year to get Ramos' endorsement. De Villa was widely believed to be the preferred candidate of President Fidel V. Ramos, due to their long association in the Philippine Constabulary, shared experience in the EDSA Revolution, and appointment as Secretary of National Defense. However, in December 1997, Ramos endorsed House Speaker Jose de Venecia, Jr., who became the official presidential candidate of the party. De Villa bolted the party and formed his own party called the Partido ng Demokratikong Reporma and formed an alliance with the Lapiang Manggagawa as Reporma–LM. He chose Pangasinan Governor Oscar Orbos as his running mate and brought rebel members of Lakas to his party. Many criticized his actions, most of whom think that he basically cloned Ramos' career. In the May 11 elections, he lost to Vice President Joseph Estrada and placed sixth overall in a field of 11 candidates.
Executive Secretary
De Villa reappeared in 2001 when the second EDSA People Power Revolution escalated and influenced active officers of the Armed Forces to withdraw support to President Joseph Estrada. When President Gloria Macapagal Arroyo assumed office, she appointed de Villa as her executive secretary. He resigned from the cabinet the succeeding year citing health conditions. In the 2004 elections, he formally withdrew alliance with Arroyo and endorsed Raul Roco as president. His party did not fill any candidates other than what was endorsed by Roco. Roco however lost to the incumbent Arroyo in the elections. In July 2005, De Villa was speculated to be picked as transition president if in case the opposition successfully ousted President Arroyo and Vice PresidentNoli de Castro from their positions and form a revolutionary government. Those plans did not happen when the Arroyo impeachment was dismissed in the House of Representatives.
Personal life
As a young captain on the armed forces in the 1960s, De Villa would spend his leisure time at the Fort Bonifacio quarters of Eduardo Ermita, his classmate at the Philippine Military Academy. Also staying there was Monica "Monet" Barrica of Dipolog City, a Philippine Airlines flight attendant and niece of Ermita's wife. De Villa married Barrica in 1968, a month before shipping out to Vietnam. De Villa and Barrica had four children:
Barrica was diagnosed with stage III malignant cancer in 1990, and died in September 2006 after a 16-year struggle. Her remains was buried in the Roman Catholic Cemetery in San Juan, Batangas.