Restrepo began his legal career as a law clerk at the American Civil Liberties Union National Prison Project.

From 2006 to 2013, he served as a United States magistrate judge of the Eastern District of Pennsylvania where he presided over a variety of criminal and civil matters.

[4] On November 12, 2014, President Obama nominated Restrepo to serve as a United States Circuit Judge of the United States Court of Appeals for the Third Circuit, to the seat vacated by Anthony Joseph Scirica, who assumed senior status on July 1, 2013.

[8][9] On December 16, 2014, his nomination was returned to the President due to the sine die adjournment of the Senate.

[14] On January 3, 2019, his nomination was returned to the President under Rule XXXI, Paragraph 6 of the United States Senate.

[15] On August 12, 2020, President Donald Trump announced his intent to renominate Restrepo to serve as a Commissioner of the United States Sentencing Commission.

[16] On May 11, 2022, President Joe Biden announced his intent to nominate Restrepo to serve as a member of the United States Sentencing Commission.