IMPORTANCE In 2014, 19 999 cases of syphilis were reported in the United States. Left untreated, syphilis can progress to late-stage disease in about 15%of persons who are infected. Late-stage syphilis can lead to development of inflammatory lesions throughout the body, which can lead to cardiovascular or organ dysfunction. Syphilis infection also increases the risk for acquiring or transmitting HIV infection. OBJECTIVE To update the 2004US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults. Screening for syphilis in pregnant womenwas updated in a separate recommendation statement in 2009 (A recommendation). EVIDENCE REVIEW The USPSTF reviewed the evidence on screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents, including patients coinfected with other sexually transmitted infections (such as HIV). FINDINGS The USPSTF found convincing evidence that screening for syphilis infection in asymptomatic, nonpregnant persons at increased risk for infection provides substantial benefit. Accurate screening tests are available to identify syphilis infection in populations at increased risk. Effective treatment with antibiotics can prevent progression to late-stage disease, with small associated harms, providing an overall substantial health benefit. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).