Background.The objective of this study was to assess and compare knowledge, attitudes, and factors that influence decision-making and behavioral factors surrounding syphilis among high-risk pregnant women and prenatal care providers in the distinct settings of Kern County and East Baton Rouge Parish. Methods.Between July 2018 and January 2019, twenty in-depth interviews (10 per site) were conducted with prenatal care providers. Eight focus group discussions (5 in California and 3 in Louisiana) were held with high-risk pregnant women. All data were recorded, transcribed, and analyzed to identify emergent themes using QSR NVivo. Results. Prenatal care providers and pregnant women revealed a range of gaps in the antenatal syphilis screening and treatment process, including delayed or no prenatal care and screening, long wait times to access syphilis testing, resulting in losses to follow-up for treatment, and lack of on-site partner testing and treatment. Women reported many factors that challenged their ability to prevent sexually transmitted diseases (STDs) in the first place, and subsequently get screened and treated (if infected) during pregnancy. Main obstacles narrated were homelessness, substance use, concurrent health problems, lack of resources (e.g. transportation and insurance), and social support. Providers were aware that many of their patients faced numerous social and behavioral barriers but felt ill-equipped to intervene. Conclusion. Congenital syphilis is completely preventable with appropriate prenatal screening and treatment. Setting-specific multilevel interventions should be adapted to address the cascade of barriers to prevention, testing, and treatment of congenital syphilis in California and Louisiana.