He founded the Chicago Hospital for Women and Children alongside Mary Harris Thompson, and later helped her graduate after being rejected by Rush due to her sex.

The same year he financially aided Thompson in founding the Woman's Medical College of Chicago where he became president of the faculty and Board of Trustees.

[3] While apprenticed, Byford borrowed books and devoted his spare time to study in fields such as chemistry, physiology, and natural history, and learned Latin, Greek and French.

[2][4] After his apprenticeship, in 1837, Byford was taken into the office of Joseph Maddox, whom after eighteen months, impressed by his progress, suggested him to appear before the state's three-man examining board.

On the subject of scrofula, Byford prepared an elaborate and valuable report, in which he talked about the importance of physical and mental exercise,[2] which gained him widespread attention and added to his growing reputation, which led to him being made vice-president of the association in May, 1857.

[2] He then, in the same year, along with his colleagues Hosmer Johnson, Nathan Smith Davis, Ralph Isham, Edmund Andrews and David Rutter,[9] founded the Chicago Medical College where he received the chair of obstetrics.

[11] Byford played a substantial role in the founding of the Chicago Hospital for Women and Children, in 1865, alongside Mary Harris Thompson, whom he provided financial, professional, and psychological support.

[2] The same year, Byford financially aided Thompson to establish the Woman's Medical College of Chicago and became president of the faculty, as well as the board of trustees, and held both positions until his death.

The prominent traits of his character were simplicity and kindness, clearness of perception and practical application, with an unyielding perseverance in the pursuit of whatever he deemed attainable and right.