We encountered a case of bilateral pleural effusion associated with prostaglandin E1 (PGE1) preparation. A 75-year-old man underwent replacement surgery for an amputated hand. PGE1 was administered at 120 μg/d to maintain circulation after vascularization. From day 7 of administration, respiratory distress developed. On day 12, pleural effusion was observed bilaterally. By discontinuing PGE1 and improving hypoalbuminemia, pleural effusion resolved rapidly. This is the first case report of PGE1-induced pleural effusion; like other drug-induced pleural effusions, discontinuing the drug resulted in rapid improvement. Although a rare complication, pleural effusion has to be suspected when a patient receiving PGE1 experiences difficulty with breathing.