A 70-year-old female presented with yellow discoloration of the nail beds of all fingers and toes, as well as bilateral pleural effusions. The patient was diagnosed as having the yellow nail syndrome based on the triad of yellow nails, lymphedema, and pleural effusions. The patient's intractable bilateral pleural effusion was treated with pleurodesis using OK-432. The treatment prevented the accumulation of pleural fluid for a long period of time. Pleural effusion associated with yellow nail syndrome is thought to be difficult to treat; however, this patient's excellent clinical course suggests that pleurodesis with OK-432 could be used to treat the disease in the future.