Venoarterial (VA) extracorporeal life support (ECLS) for neonatal respiratory failure is associated with increased mortality compared with venovenous (VV) ECLS. It is unclear whether this is a causal relationship or reflects differences in baseline disease severity between infants managed with these two strategies. Our objective was to identify clinical variables associated with the preferential selection of VA over VV ECLS, as these may confound the association between VA ECLS and increased mortality. We identified documented indications for preferential VA selection through chart review. We then assessed how the presence of common indications impacted mortality. Thirty-nine cases met eligibility. Severity of hypotension/degree of inotropic support and ventricular dysfunction on echocardiogram before cannulation were the most common specific indications for preferential VA ECLS. Mortality was 12.5% when neither high inotropic support nor ventricular dysfunction was present. Mortality rose to 20% with high inotropic support and 25% with ventricular dysfunction present alone and to 50% when both were present. We conclude that severe hypotension and ventricular dysfunction before ECLS cannulation are common indications for VA ECLS that likely influence survival. Research assessing the impact of ECLS cannulation mode on survival should adjust for baseline differences between groups for these important variables.