The Royal Philanthropic Vaccine Expedition (Spanish: Real Expedición Filantrópica de la Vacuna), commonly referred to as the Balmis Expedition, was a Spanish healthcare mission that lasted from 1803 to 1806, led by Dr Francisco Javier de Balmis, which vaccinated millions^{[dubious – discuss]} of inhabitants of Spanish America and Asia against smallpox. The vaccine was transported through children: orphaned boys who sailed with the expedition.

Smallpox, a devastating disease that was endemic throughout much of the Old World, decimated the populations of the Americas after it was introduced by the Spanish conquistadors in the 1500s. By the late 16th century, smallpox had become endemic throughout Spain's holdings in the Americas and epidemics occurred periodically over the next 300 years.

In the 18th century there were scattered attempts in the colonies to use variolation, an older, less-effective method of inoculation using smallpox material. These efforts did little to mitigate the epidemics and sometimes actually increased the spread of the contagion.

In 1798, English physician Edward Jenner pioneered the use of a vaccine to immunize persons with an inoculation of cowpox material. The new vaccine was a much safer and more effective way to prevent smallpox. At the time, about 400,000 Europeans died each year from the disease which was also responsible for one-third of all cases of blindness in Europe. The use of Jenner's new vaccine spread rapidly through Europe and had a significant positive impact on the severity and frequency of smallpox epidemics.

The vaccine first reached Spain in late 1800 and by the end of 1801, several thousand persons had been vaccinated across the country. The efforts were well publicised in Spain and by 1804, dozens of papers, treatises, newspaper articles, and editorials had been published on the smallpox vaccine.

Francisco Javier de Balmis was a military physician.

In November 1794 the daughter of King Charles IV of Spain, Infanta Maria Teresa, had died from smallpox. He had heard of the vaccine discovery. Colombia and Ecuador experienced a smallpox epidemic and called on the king for supplies.

On 30 November 1803, the expedition set off from A Coruña in northwest Spain sailing on Maria Pita. It carried 22 orphan boys (aged 3 to 10) to act as carriers of the cowpox virus. The boys were necessary because the vaccine consisted of infecting patients with cowpox, which is a virus closely related to smallpox but produces a much milder disease that confers immunity to both. However, only an active infection could be transferred to successive patients, so two boys were infected with cowpox at the beginning of the voyage, with two more infected at a time as it progressed across the Atlantic and beyond. The medical staff and caretakers for the boys consisted of Balmis, a deputy surgeon, two assistants, two first-aid practitioners, three nurses, and Isabel Zendal Gómez, the rectoress of Casa de Expósitos, an A Coruña orphanage.