The Agnew Clinic by Eakins was commissioned by Dr. D. Hayes Agnew's students at the University of Pennsylvania to celebrate the seventy-year-old physician's retirement as Professor of Surgery in 1889. It was unveiled at commencement 1 May 1889. The size of the painting, the largest Eakins ever created, is 84 3/8 x 118 1/8 inches. The artist painted the work in ninety days and received a fee of $750. Its frame carries this inscription in Latin: The most experienced surgeon, the clearest writer and teacher, the most venerated and beloved man.

Dr. Agnew (1818-1892), a Pennsylvania native, was a well-respected surgeon and educator who had served in two army hospitals during the Civil War. He was best known for his competence in removing bullets, but Eakins has chosen to show him performing a lumpectomy or partial mastectomy.

The surgeon is shown standing in an enclosure, having stepped back from the operation. He is lecturing to students, faculty, and spectators seated in the operating theatre. Dr. Agnew holds a scalpel in his left hand. He is wearing a white surgical gown.

Eakins has placed the operating table with the female patient in front of Dr. Agnew. Her hair and face are visible, the ether cone just above her chin. Her right breast and arm are shown; the left breast is being operated on. A sheet covers her lower body. The sheet beneath the patient carries the inscription: University of Pennsylvania. Between Dr. Agnew and the bed we see a closed case holding the sterilized instruments. The anesthesiologist and the surgeons all wear white. Dr. Agnew's nurse, Mary Clymer, stands by the patient's waist. She is dressed in a high white cap, white apron and black dress.