The first democratic general election in Czechoslovakia was held in 1990, and he was appointed Deputy Minister of Transportation and Posts of the Slovak Government in 1991.

At the time of the split of Czechoslovakia and the establishment of an independent Slovakia (1993), he was KDH Deputy Chairman responsible for economy.

Dzurinda was appointed as prime minister for the first time in October 1998, leading five opposition parties united as the Slovak Democratic Coalition (SDK) and defeating the government of Vladimír Mečiar at the polls.

The reformist course of Dzurinda's policies was confirmed by a mandate he was given by electors in the 2002 general election to form his second government.

During this period, the budget deficit has been reduced to less than 3 percent of GDP, and it opened the door for Slovakia to join the eurozone in 2009.

SMER leader Robert Fico has formed a coalition government with Meciar's HZDS and Slota's Slovak National Party (SNS).

Mikuláš Dzurinda has been a regular MP in the National Council of the Slovak Republic since his party's defeat in the 2006 parliamentary elections.

Dzurinda has been known for his enthusiasm for cycling and especially long distance running, cultivating an image of a healthy and competitive person.

While the media routinely covered ĽS-HZDS political meetings full of anti-Dzurinda rants, the most iconic representation of this antipathy was recorded by journalist Karol Lovaš at a ĽS-HZDS meeting in support of Gustav Krajči where a large group of 70- and 80-year-old citizens repeatedly shouted the slogan "Dzurinda is a Gypsy".

He has met and talked personally to leading foreign politicians, including U.S. presidents Bill Clinton and George W. Bush, German Chancellor Gerhard Schröder, British Prime Minister Tony Blair, European Commission President Romano Prodi, NATO Secretary General Lord George Robertson, and several influential US senators and congressmen.

Under his leadership, the Visegrád Group—a co-operative grouping of the Czech Republic, Hungary, Poland and Slovakia—was revived and gained new stimuli.

Dzurinda serves on the Leadership Council for Concordia,a nonpartisan, nonprofit based in New York City focused on promoting effective public-private collaboration to create a more prosperous and sustainable future.

In 2001, as Slovakia's prime minister, he took part in the famous New York City Marathon, completing the 42.195-km course in 3 hours, 42 minutes.