<b><i>Background:</i></b> Little is known about research in Foundling Hospitals during the 18th century. <b><i>Summary:</i></b> The London “Hospital for the Maintenance and Education of Exposed and Deserted Young Children” opened in 1741, after fundraising by the former shipmaster Thomas Coram and a Charter by King George II. From 1741 to 1756, fewer than 100 infants a year were admitted by lot. With onset of the Seven Years’ War in 1756, the House of Commons resolved and financed the admission of all deserted babies. The number of admitted babies rose to 4,000 per year, and their mortality increased. The Institution was not intended as a research and teaching facility but soon became a site for gaining knowledge of young infants. Appointed physicians included Richard Conyers, William Cadogan, William Watson, and William Buchan. Their research focused on frequent conditions in the hospital’s infirmary such as scabies, fever, measles, chilblains and scorbutic eruptions, and set standards for infant care and nutrition in the English-speaking world during the 18th century. They described the dangers connected with tight swaddling, meconium purgation, artificial feeding, and the difficulty to obtain wet nurses in the big cities. A major topic was their fight against smallpox, then fatal for 80% if infected infants, and the development of an effective technique of inoculation. <b><i>Key Messages:</i></b> Research at the London Foundling Hospital differed from modern understanding of controlled clinical trials but revealed systematic, hypothesis-driven approaches in the mid-18th century. As in other Foundling Hospitals, absent parental interference facilitated innovations.