Driven by the faith of four Daughters of Charity who arrived in Indianapolis in 1881 with $34.77 in their pockets,[2] St. Vincent was built in 1974.

The hospital has grown to include six "Centers of Excellence": Women's, Children's, Orthopedics, Cardiovascular, Neuroscience and Cancer Care.

The pediatric specialists and clinical staff at the children's hospital provide care in emergency medicine, cancer and blood diseases, general surgery, cardiology, orthopedics, pulmonology, otolaryngology, rehabilitation and endocrinology.

Since 1998, former NFL quarterback Peyton Manning has had a public and private relationship with St. Vincent.

On September 5, 2007, Manning partnered with St. Vincent to announce the renaming of St. Vincent Children's Hospital to Peyton Manning Children's Hospital at St.