He then was elected Senator (1987-1992), authoring the seminal Local Government Code. As Senator, he authored and sponsored several key pieces of legislation, among them the Local Government Code of 1991, the Cooperative Code, the Philippine Sports Commission Act, the Act Creating the Autonomous Region in Muslim Mindanao, and the People’s Small-Scale Mining Act. He also authored and co-sponsored the Generic Drugs Act and the Act Establishing the Philippine Police under a Reorganized Department of Interior and Local Government.

He then launched a bid for the vice presidency in 1992, running under the Liberal Party with Jovito Salonga running for president, finishing fifth among the vice presidential candidates by garnering 9.9% of the vote. He was defeated in the 1995 national elections after running for another term for the Senate placing on number 15. He then took the case to the Supreme Court eventually winning the suit in 2004.

In 1998, he ran successfully for another term in the Senate of the Philippines, from 1998-2004. On October 2000 Senate President Franklin Drilon issued a statement about the Juetengate Scandal of President Joseph Estrada. Drilon was removed as Senate President the next month through a Senate revamp and Aquilino Pimentel, Jr. was installed as Senate President. On December 2000, an impeachment case was filed on the Senate. On January 13, 2001, Pimentel was one of those who voted in favor of the opening of the second bank envelope. Their vote was outnumbered and some of the opposition senators cried in front of Senate President Pimentel. Joseph Estrada was ousted in January by the second EDSA People Power Revolution.Pimentel occupied the Senate Presidency until the end of the regular session on June 2001.

He was reelected in the May 10, 2004 National Elections attaining the third highest number of votes nationally of nearly 80 candidates for 12 Senate seats.

As chair of the Blue Ribbon Committee, he has recommended the prosecution of top government officials of previous administrations in relation to the Expo Pilipino centennial scam and the misuse of the funds of the Retirement and Separation Benefits Systems of the Armed Forces. He has also recommended the prosecution of certain personnel of the Land Registration Administration for involvement in faking of land titles. Recently his committee also conducted series of investigations into the allegation of Governor Luis “Chavit” Singson on jueteng scandal. As Chair of the Committee on Local Government, he has supported far-reaching amendments to further strengthen the role of local government units in national development. He has also gotten senate approval to return the police to the supervision of LGUs and has authored a law to fix the date for elections of ARMM officials.

He is the president and founder of the PDP-Laban party. On April 25, 2008, Senator Pimentel authored a bill that would shift the Philippines into a Federal Republic of the Philippines.