Talc pleurodesis is a safe and effective treatment for a recurrent malignant pleural effusion. However, acute hypoxemia, pulmonary edema or acute respiratory failure can develop in a small number of patients. We report 2 patients who developed fatal hypoxemia after talc pleurodesis which was necessary the control recurrent pleural effusion. The first case was an 18-year old male diagnosed with Ewing's sarcoma with bilateral lung metastases and pleural effusion. The performance status was ECOG (Eastern Cooperative Foncology Group) grade 3. Fever along with hypoxemia and leukocytosis developed 10 hours after the second talc pleurodesis on the right side for an uncontrolled pleural effusion, The patient died from respiratory failure after 13 days. The second case was a 66-year old female diagnosed with non-small cell lung cancer with a bone metastasis. Two weeks after systemic chemotherapy, she complained of dyspnea, and a pleural effusion was observed on the right side. Her performance status was ECOG grade 3. Talc pleurodesis was performed for recurrent pleural effusion, but hypoxemia developed 6 days after pleurodesis and she died from respiratory failure 10 days after pleurodesis. In conclusion, talc pleurodesis should be performed very carefully in patients with a poor performance status, in cases with repeated pleurodesis, bilateral pleural effusion, recent chemotherapy, radiotherapy and when there are parenchymal metastatic lesions present.