IMPORTANCE: Untreated syphilis infection in pregnant women can be transmitted to the fetus (congenital syphilis) at any time during pregnancy or at birth. Congenital syphilis is associated with stillbirth, neonatal death, and significant morbidity in infants (eg, bone deformities and neurologic impairment). After a steady decline from 2008 to 2012, cases of congenital syphilis markedly increased from 2012 to 2106, from 8.4 to 15.7 cases per 100 000 live births (an increase of 87%). At the same time, national rates of syphilis increased among women of reproductive age. OBJECTIVE To update the US Preventive Services Task Force (USPSTF) 2009 recommendation on screening for syphilis infection in pregnant women. EVIDENCE REVIEW: The USPSTF commissioned a reaffirmation evidence update to identify new and substantial evidence sufficient enough to change its prior recommendation. Given the established benefits and practice of screening for syphilis in pregnant women, the USPSTF targeted its evidence review on the direct benefits of screening on the prevention of congenital syphilis morbidity and mortality and the harms of screening for and treatment of syphilis infection in pregnant women. FINDINGS: Using a reaffirmation process, the USPSTF found that accurate screening algorithms are available to identify syphilis infection. Effective treatment with antibiotics can prevent congenital syphilis and significantly decrease adverse pregnancy outcomes, with small associated harms, providing an overall substantial health benefit. Therefore, the USPSTF reaffirms its previous conclusion that there is convincing evidence that screening for syphilis infection in pregnant women provides substantial benefit. CONCLUSIONS AND RECOMMENDATION: The USPSTF recommends early screening for syphilis infection in all pregnant women. (A recommendation).