Holy Cross Hospital and its nursing school have a long history of maintaining a charitable presence in Salt Lake City's community for over a century.

The Roman Catholic Sisters of the Holy Cross have their origins in the Congregation of the Holy Cross, founded during the early 19th century by Rev. Basil Anthony Moreau in Le Mans, France. In 1843, Fr. Moreau sent four Holy Cross sisters to northern Indiana to help Holy Cross priests establish a school for boys and young men, which would later become the University of Notre Dame. The Sisters also started a local girls' school that would eventually become Saint Mary's College in Indiana.

The Sisters' ministries expanded to include health care when, during the Civil War, 80 of the 160 Sisters nursed the sick in the Midwest. During the Spanish-American War the Sisters served in army camps in Kentucky and Georgia.

An increasing number of Catholic miners needed health care in Utah. Rev. Lawrence Scanlan (later Bishop of the Salt Lake Diocese) was among those concerned for the health and welfare of miners with nowhere to go and no way to pay for medical care. Rev. Scanlan invited Sister M. Holy Cross and Sister M. Bartholomew from Saint Mary's Notre Dame in Indiana to found the Holy Cross Sisters' tradition in Salt Lake City. On 26 October 1875, the Sisters opened Saint Mary's Hospital. Doctors Allen Fowler, D. Benedict, and J. M. Benedict made up the first staff, with no salary. The hospital, located at 5th East between South Temple and First South in Salt Lake City, had room for 14 beds. Often the Sisters slept on the floor to allow space for patients.

In 1881, construction began on a new, 125-bed hospital. Holy Cross Hospital opened in 1883 at 1050 East South Temple in Salt Lake City. The nursing school was established in 1901. The school was affiliated with Saint Mary's of the Wasatch in 1931, and over 72 years the school graduated 1,056 nurses. Overcrowding encouraged administrators to build a new school at 1002 East South Temple. The cornerstone for the new building was laid in 1949, and the school was dedicated 22 October 1950.

The hospital expanded in 1932 during its 50th anniversary, and in 1937 the hospital leased land to the city for a Municipal Rose Garden. A bouquet of roses was "paid" to the hospital administrator for the annual rose rent. The "rose rent" is captured in the collection's 1954 scrapbook.

The nursing school closed in 1973, at which point nursing programs were included in university bachelor degree programs. As of April 2005, the nursing school building functioned as a medical office complex. The Sisters of the Holy Cross operated the hospital until they sold it in 1995. HealthTrust bought Holy Cross Hospital, St. Benedict's Hospital in Ogden, Holy Cross-Jordan Valley, and ten clinics along the Wasatch Front. The selling of Holy Cross Hospital followed a national trend, as large hospital networks began to dominate the healthcare industry. Holy Cross Hospital is now Salt Lake Regional Medical Center. The sacred Catholic objects from the hospital's chapel were relocated to other Catholic churches in the region, and the chapel functions as a nondenominational area for quiet reflection and prayer.

The selling of Holy Cross Hospital marked the end of an era. The Sisters of the Holy Cross continue to minister in eight different countries, working in a variety of functions as educators, nurses, and social workers. After they sold the hospital in 1995, the Sisters founded Holy Cross Ministries in Utah, where they and their coworkers offer outreach, immigration, and health care programs in Catholic parishes and schools throughout the state.