A variety of health effects can result from tattooing. Because it requires breaking the skin barrier, tattooing carries inherent health risks, including infection and allergic reactions. Modern tattooists reduce such risks by following universal precautions, working with single-use disposable needles, and sterilising equipment after each use. Many jurisdictions require tattooists to undergo periodic bloodborne pathogen training, such as is provided through the Red Cross and the U.S. Occupational Safety and Health Administration.

Dermatologists have observed rare but severe medical complications from tattoo pigments in the body, and have noted that people acquiring tattoos rarely assess health risks prior to receiving their tattoos. Some medical practitioners have recommended greater regulation of pigments used in tattoo ink. The wide range of pigments currently used in tattoo inks may create unforeseen health problems.

Since tattoo instruments come in contact with blood and bodily fluids, diseases may be transmitted if the instruments are used on more than one person without being sterilised. However, infection from tattooing in clean and modern tattoo studios employing single-use needles is rare. With amateur tattoos, such as those applied in prisons, however, there is an elevated risk of infection. To address this problem, a programme was introduced in Canada as of the summer of 2005 that provides legal tattooing in prisons, both to reduce health risks and to provide inmates with a marketable skill. Inmates were to be trained to staff and operate the tattoo parlours once six of them opened successfully.

In the United States, the Red Cross prohibits a person who has received a tattoo from donating blood for 3 months, unless the procedure was done in a state-regulated and licensed studio, using sterile technique. The District of Columbia, Georgia (until January 2025), Idaho, Maryland, Massachusetts, New Hampshire, New York, Pennsylvania, Utah and Wyoming do not have a rigorous licensing and regulation (e.g. bloodborne pathogen training) program, meaning that people who receive tattoos there are subject to the 3-month deferral regardless of the hygienic standards of the studio. Similarly, the UK does not provide certification for tattooists, and blood donations are prohibited without exception for four months following a tattoo.

Infections that can theoretically be transmitted by the use of unsterilised tattoo equipment or contaminated ink include surface infections of the skin, hepatitis B, hepatitis C, tuberculosis, and HIV. However, no person in the United States is reported to have contracted HIV via a commercially applied tattooing process. Washington state's OSHA studies have suggested that since the needles used in tattooing are not hollow, in the case of a needle stick injury the amount of fluids transmitted may be small enough that HIV would be difficult to transmit. Tetanus risk is reduced by having an up-to-date tetanus booster prior to being tattooed. According to the Centers for Disease Control and Prevention, of 13,387 hepatitis cases in the USA in 1995, 12 cases (0.09%) were associated with tattoo parlours; by comparison, 43 cases (0.32%) were associated with dentists' offices.

In 2006, the CDC reported 3 clusters with 44 cases of methicillin-resistant staph infection traced to unlicensed tattooists.

Perhaps due to the mechanism whereby the skin's immune system encapsulates pigment particles in fibrous tissue, tattoo inks have been described as "remarkably nonreactive histologically". However, some allergic reactions have been medically documented. No estimate of the overall incidence of allergic reactions to tattoo pigments exists. Allergies to latex are apparently more common than to inks; many artists will use non-latex gloves when requested. Tattoos may even trigger a positive immune response by strengthening it.^{[clarification needed]}

People who are sensitive or allergic to certain metals may react to pigments in the skin with swelling and/or itching, and/or oozing of clear fluid called serum. Such reactions are quite rare, however, and some artists will recommend performing a test patch. Because the mercury and Azo-chemicals in red dyes are more commonly allergenic than other pigments, allergic reactions are most often seen in red tattoos. Less frequent allergic reactions to black, purple, and green pigments have also been noted.^{[unreliable medical source?]} Tattoo inks contaminated with metal allergens have been known to cause severe reactions, sometimes years later, when the original ink is not available for testing; see metal allergy.