Background: Vertical transmission of Trypanosoma cruzi infection from mother to infant accounts for a growing proportion of new Chagas disease cases. However, no systematic reviews of risk factors for T. cruzi vertical transmission have been performed. Methods: We performed a systematic review of the literature in PubMed, LILACS, and Embase databases, following PRISMA guidelines. Studies were not excluded based on language, country of origin, or publication date. Results: Our literature review yielded 27 relevant studies examining a wide variety of risk factors, including maternal age, parasitic load, immunologic factors and vector exposure. Several studies suggested that mothers with higher parasitic loads may have a greater risk of vertical transmission. A meta-analysis of 2 studies found a significantly higher parasitic load among transmitting than non-transmitting mothers with T. cruzi infection. A second meta-analysis of 10 studies demonstrated that maternal age was not significantly associated with vertical transmission risk. Conclusions: The literature suggests that high maternal parasitic load may be a risk factor for congenital Chagas disease among infants of T. cruzi seropositive mothers. Given the considerable heterogeneity and risk of bias among current literature, additional studies are warranted to assess potential risk factors for vertical transmission of T. cruzi infection.