At the suggestion of Astor’s niece, JJ named his new hotel venture after the St Regis Lake in the Adirondacks, itself having been named after the monk John Francis Regis, who was known for his hospitality. Sadly, only eight years after opening the hotel, JJ died on board the Titanic and his son Vincent eventually sold it to the Duke family.

In 1927 the Dukes added a new wing to the hotel on its east side along 55th Street, doubling the capacity to over 500 rooms. Later, the famous Maxfield Parrish painting of Old King Cole was relocated from another former Astor hotel, the Knickerbocker, and became the centerpiece and namesake of the famous bar where Fernand Petiot invented the Bloody Mary.