Rationale: Postoperative chylothorax is a rare complication after pulmonary resection. Thoracic duct variations may play a key role in postoperative chylothorax occurrence and make treatment difficult. No studies in the literature have reported the successful treatment of chylothorax second to thoracic duct variation by lipiodol-based lymphangiography.Patient concerns: A 63-year-old male and a 28-year-old female with primary lung adenocarcinoma were treated by videoassisted thoracoscopic cancer resection, and suffered postoperative chylothorax. Conservative treatment was ineffective, including nil per os, persistent thoracic drainage, fatty food restriction, and somatostatin administration.Diagnosis: Postoperative chylothorax.Interventions: Patients received lipiodol-based lymphangiography under fluoroscopic guidance. Iatrogenic injuries were identified at thoracic duct variations, including an additional channel in case 1 and the lymphatic plexus instead of the thoracic duct in case 2.Outcomes: Thoracic duct variations were identified by lipiodol-based lymphangiography, and postoperative chylothorax was successfully treated by lipiodol embolizing effect.Lessons: Thoracic duct variations should be considered after the failure of conservative treatment for postoperative chylothorax secondary to pulmonary resection. Lipiodol-based lymphangiography is valuable for identifying the thoracic duct variations and embolizing chylous leakage.