Syphilis is treated with antibiotics. Injections of penicillin, either single or given over several weeks, usually cure the disease. Certain other antibiotics are effective against syphilis for patients with penicillin allergies. However, penicillin is the only option for pregnant women. A pregnant woman with syphilis who is allergic to penicillin must go through desensitization procedures (medical procedure to reduce or eliminate sensitivity to certain drugs necessary for a patient) so she may take penicillin.

Some patients have a reaction to syphilis treatment, especially those with secondary syphilis. Reactions (such as the Jarisch-Herxheimer reaction) often occur within a day after treatment, and may feel like a worsening of the syphilis symptoms, including fever, aches, headache and flu-like symptoms. The reaction passes within a day. It may be the result of so many bacteria in the body dying at the same time.

After treatment, syphilis patients should have follow-up screening tests at regular intervals (six and 12 months) or until the nontreponemal tests come back negative. Pregnant women treated for syphilis should have blood tests each month for the remainder of their pregnancy. Women who tested negative for syphilis early in their pregnancy should be retested nearer to delivery if there has been additional risk of exposure to the disease.

People treated for syphilis should abstain from sexual activity until their sores have healed completely, and they are informed by their physician that they are no longer infectious. This may take two to three months. Sexual partners should be notified of the diagnosis so they may seek medical testing and treatment. Patients diagnosed with primary syphilis should notify all sexual contacts from the previous three months.

Those with secondary syphilis should notify all partners from the past year. In the United States, physicians must report all cases of syphilis to local health authorities and the Centers for Disease Control and Prevention (CDC).

Safe sex measures that help prevent the spread of other sexually transmitted diseases (STDs) reduce the risk for syphilis transmission. These include sexual monogamy, reducing the number of sexual partners and avoiding sex with higher risk partners (those with multiple partners or intravenous drug users). Abstaining from all sexual activity is the only way to completely prevent syphilis.

Latex condoms help reduce the risk of syphilis transmission. However, condoms only protect the areas they cover. Syphilis chancres in areas not covered by a condom (e.g., scrotum, vulva or anal area) can still spread the disease. Dental dams can minimize transmission during oral sex.

The CDC recommends that pregnant women get tested for syphilis as part of their first prenatal care visit with a physician. People with other risk factors for the disease or with multiple partners may want to be tested regularly. Women should discuss their risks for all STDs with their physician, preferably a gynecologist.