When Saint Marys Hospital opened on Sept. 30, 1889, Dr. William Worrall Mayo was 70 years old. Although still energetic and sharp, the elder Dr. Mayo knew a successful hospital practice would rest with his sons. He became a consulting physician and surgeon, and Drs. Will and Charlie, without an internship or hospital practice experience, embarked on working with the Sisters to perform surgery and care for patients.

The hospital was an imposing three-story red brick building with the capacity to serve 27 patients; however, the hospital had only a dozen beds, several without mattresses. It was some time before additional beds would be available, and the sisters who worked at Saint Marys often gave up their own beds to accommodate patients. After dark, kerosene lamps lit the building, and the sisters (nurses) carried lanterns with them as they walked the floors. The hospital had an open elevator shaft, but no elevator, and at night a sister sat beside the shaft with a light to keep people from accidentally falling into it.

Dr. Charlie took responsibility for equipping the hospital's only operating room, fashioning instruments and an operating table. The top of the operating table was covered with oilcloth and had an adjustable headrest. The second-floor operating room, which had a bay window facing north for better light, was also equipped with two gaslights. The floor was slightly inclined and had a drain. In addition to the operating table, a "sponge table" was equipped with six sponge basins and four pitchers, plus a quart basin, a funnel and a vomiting bowl. A nearby instrument table included a granite bowl for the doctors to wash their hands and a specimen dish for pathological specimens. On yet another table were glass containers for sponges, airtight containers for absorbent cotton and gauze, an ether cone, iodoform (for antiseptic dressings), Cosmoline (for petroleum jelly), hypodermic syringe, morphine, brandy, alcohol, glycerin, sweet and castor oil, spirits of ammonia, aqua ammonia, camphor, nitric acid, iodine, laudanum and antiseptic tablets.

The Sisters furnished the patient rooms with cots and muslin sheets and pillowcases. Dr. W.W. Mayo trained the hospital's first nurse anesthetist, Edith Graham, who had married Dr. Charlie in 1893.