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Congenital syphilis (CS) has been rapidly re-emerging as a public health crisis across North America. The present standard of care treatment for CS involves a 10-day hospitalisation for intravenous penicillin G, which is costly for healthcare systems and families. Given these costs and the frequency of their application, the purpose of this study was to locate the evidence upon which the standard of care for CS has been founded and to assess its quality.A search of Embase and MEDLINE was conducted, and a total of 398 publications were evaluated for inclusion in this study. 54 publications met the inclusion criteria. Quality of data was appraised using the Oxford Centre for Evidence-Based Medicine (OCEBM) levels of evidence 2011 and the American Academy of Family Physicians grades of strength of recommendation taxonomy (SORT). Levels of evidence in OCEBM 2011 are assigned a number from 1 (highest quality) to 5 (weakest). The strength of recommendations in SORT is assigned a letter from A (strongest recommendation) to C (weakest). Level 5 evidence and grade C recommendations were the most abundant results in this study. Additionally, the most common treatment regimens reported were intramuscular penicillin administration, in doses of 50 000–75 000 units/kg, for a duration of 10–14 days. Systematic statistical analyses could not be applied to the results due to inconsistency and arbitrary changes of treatment within the individual constituent studies. The results affirmed a gap in high-quality primary evidence behind the treatment of CS. Supporting literature is based on expert opinion, consensus and non-randomised studies. Overall, this project underscores the need for high-quality randomised controlled trials to understand the limitations of the current standard of care and to confirm the need for a 10-day course of intravenous penicillin G in hospital.