McKennan Hospital's first few decades were a time of rapid growth. Admissions went from 500 in 1912 to 1,333 in 1918. The first addition was completed in 1919, expanding the patient capacity to 131 beds. The second addition, a new chapel, was made in 1931. In 1943, the top floor was remodeled and the walls extended upward. The patient capacity was increased to 171 beds as new operating rooms, lab facilities and an expanded pediatrics department were added.
McKennan Hospital also served as a hub for regional medical activity. In 1919, a group of McKennan Hospital medical staff physicians began the Sioux Falls Clinic. In 1920, a McKennan physician conducted the first public clinic for children and introduced an immunization program against diphtheria. The early 1920's saw the first "Clinic Day" held at McKennan Hospital, for the exchange of ideas among physicians, and in 1936, the McKennan Auxiliary was organized. The Presentation School of Nursing, established shortly after the hospital opened, became known for excellence in education and training. The school was made part of the U.S. Cadet Corps program in 1943.