This study tested the hypothesis that pediatric patients who develop chylothorax (CTX) after surgery for congenital heart disease (CHD) have an elevated incidence and risk profile for central venous thrombosis (CVT). We evaluated 30 patients who developed CTX after surgery for CHD. All but one CTX patient were surgery-, anatomy-, and age-matched with two controls (NON-CTX) to compare their relative risk and incidence of CVT. Using conditional logistic regression analyses, CTX development was associated with significantly longer ventilator dependence (14.8 ± 10.9 vs. 6.1 ± 5.9 days, p = 0.003) and a non-significant trend towards more days of central venous catheters (CVC) (19.1 ± 16.6 vs. 12.2 ± 10.0 days; p = 0.16) when comparing the period prior to CTX development with the entire hospitalization in NON-CTX patients. CTX development was associated with a significantly elevated mortality risk (Odds Ratio 6.2, 95% CI 1.3–30.9). Minimum and mean daily central venous pressures were significantly higher in the CTX group. Post operative need for extracorporeal membrane oxygenation conferred an increased risk of CTX development in this sample of patients (Odds Ratio 9.9, 95% CI 2.2–44.8). Incidence of documented CVT was 26.7% in the CTX group versus 5.1% in the NON-CTX group. Prospective screening for CVT risk and formation, combined with early removal of CVC may help reduce the incidence of CTX.