Superior vena cava (SVC) flow has been considered a surrogate marker of systemic blood flow in neonates. We conducted a systematic review to evaluate the association between low SVC flow recorded during the early neonatal period and neonatal outcomes. We searched the following databases (until December 9, 2020; updated October 21, 2022): PROSPERO, OVID Medline, OVID EMBASE, Cochrane Library (CDSR and Central), Proquest Dissertations and Theses Global, and SCOPUS using controlled vocabulary and key words representing the concepts "superior vena cava" and "flow" and "neonate." Results were exported to COVIDENCE review management software. The search retrieved 593 records after the removal of duplicates, of which 11 studies (nine cohorts) met the inclusion criteria. The majority of the studies included infants born at <30 weeks of gestation. The included studies were assessed as high risk of bias in terms of the incomparability of the study groups, with infants in the low SVC flow group noted to be more immature than those in the normal SVC flow group or subjected to different cointerventions. We did not conduct meta-analyses in view of the significant clinical heterogeneity noted in the included studies. We found little evidence to suggest that SVC flow in the early neonatal period is an independent predictor for adverse clinical outcomes in preterm infants. Included studies were assessed at high risk of bias. We conclude that SVC flow interpretation for prognostication or for making treatment decisions should be restricted to the research setting for now. We highlight the need for strengthened methods in future research studies. KEY POINTS: · We studied whether low SVC flow in the early neonatal period is a marker for adverse outcomes in preterm infants.. · There is insufficient evidence to conclude that low SVC flow is a valid predictor of adverse outcomes.. · There is insufficient evidence to conclude that SVC flow-directed hemodynamic management improves clinical outcomes..