On February 18, 1868, Margaret Louisa was married to Elliott Fitch Shepard (1833–1893) in the Church of the Incarnation in New York.
 He was the son of Fitch Shepard and Delia Maria Dennis.
Shepard was a lawyer, banker, and owner of the Mail and Express newspaper, as well as a founder and president of the New York State Bar Association.
 Together, they had five daughters and one son:
Florence Shepard (1869–1869), who died young.

Maria Louise Shepard (1870–1948), who married William Jay Schieffelin (1866–1955), a descendant of John Jay.

Edith Shepard (1872–1954), who married Ernesto Fabbri (1874–1943).

Margaret Shepard (1873–1895), who died unmarried of pneumonia.

Alice Louise Shepard (1874–1950), who married Dave Hennen Morris (1872–1944), the U.S. Ambassador to Belgium and son of John Albert Morris.

Elliot Fitch Shepard, Jr. (1877–1927), who married Esther Potter, and after their divorce, Eleanor Leigh Terradell (1882–1962).

Margaret died at her apartment on 998 Fifth Avenue in Manhattan on March 3, 1924.
She is buried in the Vanderbilt Private Section, a burial ground just outside the Vanderbilt Mausoleum Moravian Cemetery, Staten Island.
 At her death, she left over $5,000,000 in trust to her daughters.
 She donated $180,000 to charities, $20,000 to each of her sixteen grandchildren, and $100,000 to the Scarborough Presbyterian Church, in addition to the $100,000 left to the Church upon her husband's death in 1893.
On February 18, 1868, Margaret Louisa was married to Elliott Fitch Shepard (1833–1893) in the Church of the Incarnation in New York.  He was the son of Fitch Shepard and Delia Maria Dennis. Shepard was a lawyer, banker, and owner of the Mail and Express newspaper, as well as a founder and president of the New York State Bar Association.  Together, they had five daughters and one son:
Florence Shepard (1869–1869), who died young.
Maria Louise Shepard (1870–1948), who married William Jay Schieffelin (1866–1955), a descendant of John Jay.
Edith Shepard (1872–1954), who married Ernesto Fabbri (1874–1943).
Margaret Shepard (1873–1895), who died unmarried of pneumonia.
Alice Louise Shepard (1874–1950), who married Dave Hennen Morris (1872–1944), the U.S. Ambassador to Belgium and son of John Albert Morris.
Elliot Fitch Shepard, Jr. (1877–1927), who married Esther Potter, and after their divorce, Eleanor Leigh Terradell (1882–1962).
Margaret died at her apartment on 998 Fifth Avenue in Manhattan on March 3, 1924. She is buried in the Vanderbilt Private Section, a burial ground just outside the Vanderbilt Mausoleum Moravian Cemetery, Staten Island.  At her death, she left over $5,000,000 in trust to her daughters.  She donated $180,000 to charities, $20,000 to each of her sixteen grandchildren, and $100,000 to the Scarborough Presbyterian Church, in addition to the $100,000 left to the Church upon her husband's death in 1893.
Margaret Louisa Vanderbilt Shepard