[5] In 2006, de Guindos was appointed advisor for Lehman Brothers in Europe[6][7] and director of its subsidiary bank in Spain and Portugal, where he remained until the collapse and declaration of bankruptcy of the latter in 2008.

Finally, and in a largely ceremonial role, he was appointed as a professor of finance at the PwC and IE Financial Sector Center of IE Business School (Madrid), between 2010 and 2012, before joining as a minister.

De Guindos has served as economy minister in Rajoy's centre-right government since it took office in December 2011 and is credited with steering Spain to economic recovery following the euro zone's 2009–2014 crisis.

[14] At the time, analysts said that if Spain had nominated de Guindo's predecessor Elena Salgado for the board, she would have been a shoo-in instead of Mersch who was ultimately elected.

[16][17] In August 2014, German Chancellor Angela Merkel, who also belongs to the EPP political bloc, gave him her backing in his bid to succeed Jeroen Dijsselbloem as leading the Eurogroup from mid-2015;[18] Securing the Eurogroup post for de Guindos was a key political goal for Rajoy, who hoped that his appointment will cement perceptions both at home and abroad that Spain has emerged from crisis and can be taken seriously once again at international level.

[26] In 2017, de Guindos was widely seen as a natural successor to replace Jeroen Dijsselbloem as next chairman of the Eurogroup but he ruled himself out early in favour of an expected candidacy to become Vice-president of the European Central Bank.

[27] After Ireland withdrew the candidacy of Philip Lane in February 2018, German Finance Minister Peter Altmaier was one of the first among his peers to openly endorse de Guindos.