With the founding of Ville-Marie in 1642 and the arrival of Jeanne Mance, a secular nurse, a little clinic was opened inside the fort. The first Hôtel-Dieu hospital was built in 1645. Located in Vieux-Montréal, this first hospital had five rooms and six beds. For two centuries, Hôtel-Dieu was the only French-speaking hospital in Montréal.
In the 19th century, the number of patients quickly increased, due to population growth and numerous epidemics such as cholera and typhus. Having become too cramped, the Hôtel-Dieu was relocated to the foot of Mont Royal, at the corner of avenue des Pins and rue Saint-Urbain, in 1860-1861. For nearly four centuries, the very first hospital in Montréal treated hundreds of thousands of patients, providing high-quality health care services there.