A marriage between Henry II and Margherita Gonzaga, her being the niece of the new Queen of France (Marie de' Medici), would ally the Lorraine not only with the House of Gonzaga but also work as a proxy alliance between Lorraine and France, and that is how it was perceived at the French royal court as well.

[3] In September 1605, Henry IV of France and Vincenzo I Gonzaga agreed to make a mutual alliance with Lorraine through Margherita, and in February 1606 the marriage contract was signed in Paris by the agents of the bride and groom.

In May 1608 Henry II succeeded his father as Duke of Lorraine and Margherita Gonzaga became Duchess.

She was described as unattractive with a heavy chin and a big nose and was said to look older than her years, but also as strong and healthy.

She was a spendthrift who loved luxury and reportedly loved to give expensive gifts, bought twelve shoes every months and continued to expand her stable with new horses; she was an enthusiastic hostess who preferred to stay in the Ducal Palace of Nancy, where she often arranged balls.

[5] In the absence of a son, Margherita and Henry attempted to secure the inheritance of Lorraine and Bar for their eldest daughter Nicole.