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Congenital syphilis is a significant cause of adverse pregnancy outcomes. In South Africa, rural clinics perform antenatal screening offsite, but unreliable transport and poor client follow up impede effective treatment. We compared 3 syphilis screening strategies at rural clinics: onsite rapid plasma reagin (RPR), onsite treponemal immunochromatographic strip (ICS) test, and the standard practice offsite RPR with Treponema pallidum hemagglutination assay (RPR/TPHA).Eight rural clinics performed the onsite RPR and ICS tests and provided immediate treatment. Results were compared with RPR/TPHA at a reference laboratory. Chart reviews at 8 standard practice clinics established diagnosis and treatment rates for offsite RPR/TPHA.Seventy-nine (6.3%) of 1,250 women screened onsite had active syphilis according to the reference laboratory. The onsite ICS resulted in the highest percentage of pregnant women correctly diagnosed and treated for syphilis (89.4% ICS, 63.9% onsite RPR, 60.8% offsite RPR/TPHA). The onsite RPR had low sensitivity (71.4% for high-titer syphilis). The offsite approach suffered from poor client return rates. One percent of women screened with the ICS may have received penicillin unnecessarily. There were no adverse treatment outcomes.The onsite ICS test can reduce syphilis-related adverse outcomes of pregnancy through accurate diagnosis and immediate treatment of pregnant women with syphilis.