
After his discharge from the Butler Sanatorium in 1886, Halsted was invited by William Welch to conduct research in the newly-formed pathological laboratory at Johns Hopkins in an effort to restart his career. Working with Franklin P. Mall, he perfected techniques for intestinal suture and wound healing in dogs. He developed methods which consisted of strict aseptic technique, gentle handling of tissue, use of fine silk suture material, small stitches and low tension on the tissue, and complete closure of wounds whenever possible. These basic methods transformed the practice of surgery, making it safer and more effective.
When The Johns Hopkins Hospital opened in 1889, the original person chosen as surgeon-in-chief resigned without ever coming to Baltimore. Halsted was asked to serve as acting surgeon-in-chief, and was later appointed first surgeon-in-chief. He was named first professor of surgery of the Johns Hopkins University School of Medicine when it opened in 1893.
In 1890, Halsted introduced the use of rubber gloves at Johns Hopkins when his scrub nurse, Caroline Hampton, developed severe dermatitis from immersing her hands in mercuric chloride which was the standard pre-surgery sterilizing practice of the time. Halsted arranged to have the Goodyear Rubber Company make some thin rubber gloves for her use. They were married later that year. In 1896, the use of rubber gloves became the standard in surgery when Dr. Joseph Bloodgood and others began to routinely wear them for aseptic purposes.
Renowned as a surgeon and as a clinical teacher, Halsted combined experimental work in physiology and pathology to innovate surgical techniques for the thyroid and parathyroid glands, blood vessels, breast cancer, and hernia. He was instrumental in launching the subspecialty divisions of orthopaedics, otolaryngology, urology, and roentgenology at Johns Hopkins. One of his greatest legacies is his success in training surgeons and in establishing the first formal surgical residency training program. A significant number of his residents went on to lead surgical departments at other institutions, where they promoted his techniques and set up residency programs modeled on what Halsted created at Johns Hopkins.