His Garmin-Sharp team said the 37-year-old suffered “multiple contusions and abrasions” in a crash Friday on Stage 7 from Montpellier to Albi.
Vande Velde was riding with severe back pain and a blood clot in his neck muscle sustained in an earlier crash on Stage 5.
The team says the accumulation of injuries from two crashes in three days forced him out of the Tour.
It is the third time the American has failed to finish the Tour.
In 2001, Vande Velde crashed out during a wet team time trial stage and three years ago he had to abandon after falling in a mass pile-up on stage three.
Source: Associated Press