A 77-year-old man was admitted to the hospital with fever, anorexia, and a bilateral pleural effusion, with more effusion on the right side. Drug-induced lupus erythematosus (DILE) was suspected due to the presence of lymphocyte-dominant exudative pleural effusions, a high level of antinuclear antibodies, and negative anti-double stranded deoxyribonucleic acid antibodies. A thoracoscopy revealed white thickening of the parietal pleura and the tissue showed non-specific inflammation. Clopidogrel, which had been started two years and two months earlier, was suspected as the cause of the DILE. Due to the patient’s condition, there was no time to wait and see the effect of simply withdrawing the drug. The patient was treated with steroids and was found to be positive for anti-histone antibodies after treatment initiation. Consequently, his condition improved and the pleural effusions resolved after completion of the steroid course. This is a notable case as DILE due to clopidogrel has never been reported so far.