On December 13, 1809, McDowell was called to see Jane Todd Crawford in Green County, Kentucky, 60 miles (97 km) from Danville. Her physicians thought that Mrs. Crawford was beyond term pregnant. McDowell diagnosed an ovarian tumor. Crawford begged him to keep her from a slow and painful death. He then described her condition and that an operation for cure had never been performed. He said that the best surgeons in the world thought it impossible. Crawford said she understood and wanted to proceed. McDowell told her he would remove the tumor if she would travel to his home in Danville. She agreed and rode the sixty miles on horseback.
On Christmas morning, 1809, McDowell began his operation. The surgery was performed without benefit of anesthetic or antisepsis, neither of which was then known to the medical profession. The tumor McDowell removed weighed 22.5 pounds (10.2 kg). He determined that it would be difficult to remove completely, so he tied a ligature around the fallopian tube near the uterus and cut open the tumor. He described the tumor as the ovarium and fimbrious part of the fallopian tube very much enlarged. The whole procedure took 25 minutes. Crawford made an uncomplicated recovery. She returned to her home in Green County 25 days after the operation and lived another 32 years. This was the first successful removal of an ovarian tumor in the world.