On March 22, 2008, the, PPP nominated Gilani, for the post of Prime Minister. Premiership

On March 22, 2008, the PPP nominated Gilani for the post of Prime Minister. PPP completed consultations with coalition partners about the Prime Minister and its allies endorsed the nomination. The formal announcement of the name of Prime Minister was expected to be made that night.

On March 22 at 9:38 pm Islamabad, (1638 GMT), he was officially announced by PPP as its candidate for the premiership of the country.

Many analysts said that they would not be surprised if Zardari succeeded Gilani after a few months. It was reported on March 24, 2008, that Zardari said he was not interested in the job of Prime Minister and that Gilani would serve until 2013 in the position. Speculation that Zardari might be gunning for the premiership grew stronger when he picked the less popular Gilani over Makhdoom Amin Fahim, President of the PPP. Fahmida Mirza, the newly-elected Speaker of the Assembly, insists there is no plan to replace Gilani. She added, however, that if Gilani did not do a good job, all options were open.

On March 24, 2008, Gilani was elected as Prime Minister by Parliament, defeating his rival, Chaudhry Pervaiz Elahi of the PML-Q, by a score of 264 to 42. He was sworn in by Musharraf on the next day On March 29, he won a unanimous vote of confidence in Parliament.

On the same day, following the vote of confidence, Gillani announced the programme for the first 100 days of his administration. Some of the points he announced were:

Frontier Crimes Regulations and Industrial Relations Order repealed
A “truth and reconciliation commission” proposed
PM House budget cut by 40 percent
Special counters at airports for parliamentarians to be removed
No money to be spent on the renovation of government buildings and residences
A freedom of information law to be framed, while PEMRA will be made a subsidiary of the information ministry
Talks will be initiated with extremists who lay down arms and ‘adopt the path of peace’
A new package for tribal areas promised
Employment commission to be set up
Madressah authority to implement a uniform curriculum
One million housing units to be built annually for low-income groups
Irrigation channels to be bricklined.
A lifting of the bans on elected labor and students' unions.
The first part of Gillani's Cabinet was sworn in on March 31. Of the 24 ministers sworn in on this occasion, 11 were members of the PPP, nine were members of the Pakistan Muslim League (N) (PML-N), two were members of the Awami National Party, one was from Jamiat Ulema-e-Islam, and one came from the Federally Administered Tribal Areas. Other appointments were expected to follow.

On May 13, 2008, the PML (N) ministers resigned from Gillani's government due to a disagreement related to the reinstatement of judges whom Musharraf removed from office in 2007. Zardari, hoping to preserve the coalition, told Gillani to reject the resignations.

At the close of 2008, Pakistan's The Financial Daily conducted a public poll on its website; respondants entered the names of their favourite personalities for the year, and Gillani was named among the top 50.