Use through the 19th century

Even after the humoral system fell into disuse, the practice was continued by surgeons and barber-surgeons. Though the bloodletting was often recommended by physicians, it was carried out by barbers. This led to the distinction between physicians and surgeons. The red-and-white-striped pole of the barbershop, still in use today, is derived from this practice: the red symbolizes blood while the white symbolizes the bandages. Bloodletting was used to "treat" a wide range of diseases, becoming a standard treatment for almost every ailment, and was practiced prophylactically as well as therapeutically.

A number of different methods were employed. The most common was phlebotomy, or venesection (often called "breathing a vein"), in which blood was drawn from one or more of the larger external veins, such as those in the forearm or neck. In arteriotomy, an artery was punctured, although generally only in the temples. In scarification (not to be confused with scarification, a method of body modification), the "superficial" vessels were attacked, often using a syringe, a spring-loaded lancet, or a glass cup that contained heated air, producing a vacuum within (see fire cupping). There was also a specific bloodletting tool called a scarificator, used primarily in 19th century medicine. It has a spring-loaded mechanism with gears that snaps the blades out through slits in the front cover and back in, in a circular motion. The case is cast brass, and the mechanism and blades steel. One knife bar gear has slipped teeth, turning the blades in a different direction than those on the other bars. The last photo and the diagram show the depth adjustment bar at the back and sides.

Leeches could also be used. The withdrawal of so much blood as to induce syncope (fainting) was considered beneficial, and many sessions would only end when the patient began to swoon.

William Harvey disproved the basis of the practice in 1628, and the introduction of scientific medicine, la méthode numérique, allowed Pierre Charles Alexandre Louis to demonstrate that phlebotomy was entirely ineffective in the treatment of pneumonia and various fevers in the 1830s. Nevertheless, in 1838, a lecturer at the Royal College of Physicians would still state that "blood-letting is a remedy which, when judiciously employed, it is hardly possible to estimate too highly", and Louis was dogged by the sanguinary Broussais, who could recommend leeches fifty at a time. Some physicians resisted Louis' work because they "were not prepared to discard therapies 'validated by both tradition and their own experience on account of somebody else's numbers'."

Bloodletting was used to treat almost every disease. One British medical text recommended bloodletting for acne, asthma, cancer, cholera, coma, convulsions, diabetes, epilepsy, gangrene, gout, herpes, indigestion, insanity, jaundice, leprosy, ophthalmia, plague, pneumonia, scurvy, smallpox, stroke, tetanus, tuberculosis, and for some one hundred other diseases. Bloodletting was even used to treat most forms of hemorrhaging such as nosebleed, excessive menstruation, or hemorrhoidal bleeding. Before surgery or at the onset of childbirth, blood was removed to prevent inflammation. Before amputation, it was customary to remove a quantity of blood equal to the amount believed to circulate in the limb that was to be removed.

There were also theories that bloodletting would cure "heartsickness" and "heartbreak". A French physician, Jacques Ferrand wrote a book in 1623 on the uses of bloodletting to cure a broken heart. He recommended bloodletting to the point of heart failure (literal).

Leeches became especially popular in the early nineteenth century. In the 1830s, the French imported about forty million leeches a year for medical purposes, and in the next decade, England imported six million leeches a year from France alone. Through the early decades of the century, hundreds of millions of leeches were used by physicians throughout Europe.

Bloodletting was also popular in the young United States of America, where Benjamin Rush (a signatory of the Declaration of Independence) saw the state of the arteries as the key to disease, recommending levels of bloodletting that were high even for the time. George Washington asked to be bled heavily after he developed a throat infection from weather exposure. Within a ten-hour period, a total of 124–126 ounces (3.75 liters) of blood was withdrawn prior to his death from a throat infection in 1799.

One reason for the continued popularity of bloodletting (and purging) was that, while anatomical knowledge, surgical and diagnostic skills increased tremendously in Europe from the 17th century, the key to curing disease remained elusive, and the underlying belief was that it was better to give any treatment than nothing at all. The psychological benefit of bloodletting to the patient (a placebo effect) may sometimes have outweighed the physiological problems it caused. Bloodletting slowly lost favour during the 19th century, after French physician Dr. Pierre Louis conducted an experiment in which he studied the effect of bloodletting on pneumonia patients. A number of other ineffective or harmful treatments were available as placebos—mesmerism, various processes involving the new technology of electricity, many potions, tonics, and elixirs. Yet, bloodletting persisted during the 19th century partly because it was readily available to people of any socioeconomic status.