Chylothorax complicates congenital heart disease (CHD) surgery and may be associated with significant morbidity. Etiology of chylothorax is multifactorial, and it has been associated with deep venous thrombosis and obstruction from central venous lines (CVLs) in patients without CHD. We sought to determine whether CVL insertion site was associated with the occurrence of chylothorax in infants after cardiac surgery. Retrospective cohort of patients less than one year of age who underwent CHD surgery requiring cardiopulmonary bypass from 2008 to 2012. Chylothorax was identified by clinical diagnosis and/or laboratory findings (milky effusion, fluid with >100 mg/dL of triglycerides and/or >80% of lymphocytes). Central venous lines insertion site was verified by reviewing procedure notes and chest x-rays. Internal jugular (IJ), subclavian vein, and femoral vein (FV) CVLs were used during the study period. Three hundred and ninety-two patients were included (mean age 97 days, mean weight 4.5 kg). Sixty-two (15.8%) of these patients developed chylothorax after surgery. Patients with chylothorax had longer bypass time (P = .02), longer cross-clamp time (P = .03), higher RACHS-1 category (P = .03), and more frequent upper body CVLs (IJ or subclavian vein; P = .03). There was no significant association with age, gender, preoperative weight, and height. Multivariate analysis showed patients with a CVL in the upper body (IJ or subclavian vein) were almost two times more likely to develop a chylothorax than patients who had FV CVL, (odds ratio = 1.9, 95% confidence interval = 1.05-5.60; P = .044). Postoperative chylothorax is associated with line insertion in the upper body (subclavian vein and IJ). Avoidance of CVLs in these locations may decrease its incidence. © 2014, SAGE Publications. All rights reserved.