The Santa Margarita Invitational Handicap is an American Grade I Thoroughbred horse race run annually in early March at Santa Anita Park in Arcadia, California. An invitation race for fillies and mares age four and older, it is contested on dirt over a distance of one and one-eighths miles.

Inaugurated in 1935, the race was open to all horses age three and older until 1938 when it was restricted to filles and mares. Since inception, the Santa Margarita Handicap has been raced at various distances. There was no race from 1942 through 1944 as a result of World War II. The Santa Margarita Handicap was run in two divisions in 1964. The first time it was run as an invitational event was in 1968.