By 1912, through investments, the endowment had increased to more than $2 million. The trustees bought property near Forest Park and hired the renowned architect Theodore Link- best known for his design of St. Louis Union Station -- to design the hospital building.
Before ground was ever broken, Barnes Hospital entered into a contract to be the teaching hospital for the Washington University School of Medicine, ensuring that the hospital would be staffed by Washington University faculty and would serve as a home for medical education, research and leading-edge medical care. The affiliation between Washington University and Barnes Hospital was "vital to fulfill the three principal functions of an ideal hospital -- care of the sick, the adequate training of medical men of the future and the advancement of medical knowledge," said Methodist Bishop Eugene Hendrix. The affiliation influenced Link to add laboratories, exam rooms and operating rooms to the hospital's design.
Barnes Hospital opened Dec. 7, 1914, with 250 beds and 26 patients.
From the hospital's first birth (a baby girl born on Dec. 9) and first surgery (an appendectomy performed by surgeon-in-chief Dr. Fred Murphy, assisted Dr. Ernest Sach, the first full-time professor of neurosurgery in the United States) excellence in patient care and innovative treatment have marked the hospital's history.
Barnes Hospital dealt with the deadly Spanish influenza epidemic of 1918. With more than 700 patients admitted during the peak of the outbreak, Barnes had a death rate of less than four percent, remarkable for the Spanish flu.