Summary: To clarify the management and treatment for the refractory cases of secondary spontaneous pneumothorax (SSP), we analyzed the clinical features in SSP complicating three cases of advanced silicosis, and discussed the available treatment. All three cases were males of age ranging from 60 to 70 years, and had silicosis with massive progressive fibrosis (PMF), classified as type 4 (PR4) according to the ILO guidelines. There was no correlation between the onset of SSP and the smoking habit, or the duration of the occupational exposure to silica. In a total of ten episodes of SSP, a refractory episode occurred in each of the three patients. No surgical treatment was possible because of some complications. Therefore, we administered conservative treatments under mechanical ventilation. The conservative treatments used were tube drainage with suction in each episode and pleurodesis by the combination of minocycline and OK-432 in one case. Approximately one month was the average time required for the air leak cessation. A significant decline in arterial oxygen tension (Pa02) was observed after the treatment of one case, suggesting further respiratory deterioration. These results imply that the more aggressive treatments for refractory SSP should be limited because of the patient status and progression. More information might be required before performing these options safely and effectively.