From 2004 to 2005 Pofalla was deputy chairman of the CDU/CSU's parliamentary group in the Bundestag under the leadership of Angela Merkel, and served as the Secretary General of the CDU from 2005 to 2009.

In September 2011 he seriously insulted Wolfgang Bosbach, senior group leader of the CDU/CSU-group in the Bundestag after an in-house discussion about the enhancement of the European Financial Stability Facility.

[2] In the negotiations to form a coalition government following the 2013 federal elections, Pofalla was part of the 15-member leadership circle chaired by Merkel, Horst Seehofer and Sigmar Gabriel.

At Deutsche Bahn, Pofalla took up a "specially created lobbying post" said to carry compensation of more than a million euros a year.

[7] In April 2023, Pofalla was one of the 22 personal guests at the ceremony in which Angela Merkel was decorated with the Grand Cross of the Order of Merit for special achievement by President Frank-Walter Steinmeier at Schloss Bellevue in Berlin.

"[14] Pofalla caused controversy when German tabloid Bild revealed that he had bought premium Montblanc writing materials worth 3,307.61 euros for his MP office at the expense of the Bundestag in 2009; at the time, it was the highest recorded order by any parliamentarian.