We successfully treated a case of in-stent restenosis, which presented on 6 occasions, resulting in frequent acute inferior wall myocardial infarctions, using a drug-eluting stent. This case demonstrates that drug-eluting stents offer the promise of an effective treatment for frequent in-stent restenosis, and importantly, that the underexpansion of a drug-eluting stent heightens the risk of acute or subacute stent thrombosis.