Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.

Common side effects include nausea, vomiting, diarrhea, and loss of appetite. It often turns urine, sweat, and tears a red or orange color. Liver problems or allergic reactions may occur. It is part of the recommended treatment of active tuberculosis during pregnancy, though its safety in pregnancy is not known. Rifampicin is of the rifamycin group of antibiotics. It works by decreasing the production of RNA by bacteria.

Rifampicin was discovered in 1965, marketed in Italy in 1968, and approved in the United States in 1971. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies rifampicin as critically important for human medicine. It is available as a generic medication. Rifampicin is made by the soil bacterium Amycolatopsis rifamycinica.

Rifampicin is used for the treatment of tuberculosis in combination with other antibiotics, such as pyrazinamide, isoniazid, and ethambutol. For the treatment of tuberculosis, it is administered daily for at least six months. Combination therapy is used to prevent the development of resistance and to shorten the length of treatment. Resistance of Mycobacterium tuberculosis to rifampicin develops quickly when it is used without another antibiotic, with laboratory estimates of resistance rates from 10⁻⁷ to 10⁻¹⁰ per tuberculosis bacterium per generation.

Rifampicin can be used alone in patients with latent tuberculosis infections to prevent or delay the development of active disease because only small numbers of bacteria are present. A Cochrane review found no difference in efficacy between a 3- to 4-month regimen of rifampicin and a 6-month regimen of isoniazid for preventing active tuberculosis in patients not infected with HIV, and patients who received rifampicin had a lower rate of hepatotoxicity. However, the quality of the evidence was judged to be low. A shorter 2-month course of rifampicin and pyrazinamide had previously been recommended but is no longer recommended due to high rates of hepatotoxicity.

Rifampicin should be taken on an empty stomach with a glass of water. It is generally taken either at least one hour before meals or two hours after meals.

Rifampicin is also used to treat nontuberculous mycobacterial infections including leprosy (Hansen's disease) and Mycobacterium kansasii.

With multidrug therapy used as the standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid causing drug resistance.^{[citation needed]}