Blackwell encountered further resistance in her attempts to set up a practice. When New York City's hospitals refused to offer her any post, she eventually opened up a small dispensary of her own in a slum district. Her perseverance once again paid off, for in 1859 the now greatly enlarged dispensary was incorporated as the New York Infirmary for Women and Children. By 1868, after consultation with Florence Nightingale, she was able to open up the Woman's Medical College at the infirmary, which remained in operation for thirty-one years. During the American Civil War she performed valuable service by helping to organize the Woman's Central Association of Relief, which selected and trained nurses for the war, and the U.S. Sanitary Commission.
In 1869, Blackwell moved permanently to England, where she established a successful private practice and was appointed professor of gynecology at the London School of Medicine for Women. She retired in 1907.