Following her graduation, Cole interned at Elizabeth Blackwell's New York Infirmary for Indigent Women and Children where she was assigned the task of going into tenements to teach prenatal care and hygiene to women. Cole went on to briefly practice medicine in South Carolina before returning to Philadelphia. In 1873 Cole opened a Women's Directory Center with Dr. Charlotte Abbey which provided medical and legal services to disadvantaged women and children. In January 1899, Cole was appointed superintendent of a home run by the Association for the Relief of Destitute Colored Women and Children in Washington, D.C. The association's 1899 annual report stated that Cole possessed "all the qualities essential to such a position-ability, energy, experience, tact." A subsequent report noted that:
