From 2005 to 2007, he was successively Secretary of State for Health Insurance and Senior and Minister for Health. He led the reform of health insurance scheme, managed the 2006 chikungunya disease outbreak in La Reunion Island and successfully achieved the smoking ban in all public places.

In 2007, Xavier Bertrand served as the official spokesperson for Nicolas Sarkozy's presidential campaign and became Minister of Labour, Social Affairs, Family and Solidarity. He modernized labor contract law, relaxed working-time rules, ended the “special regimes” for public-sector pensions and implemented the minimum service system in public transportation.

From January 2009 to November 2010, Xavier Bertrand was the General Secretary of the Union pour un Mouvement Populaire (UMP), France governing party.

Since November 2010, Xavier Bertrand is Minister of Labour, Employment and Health.

Xavier Bertrand is Mayor of Saint-Quentin (Aisne).