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The optimal approach to in-stent restenosis (ISR) within a drug eluting stent (DES) remains uncertain. The Rotterdam research registry reported a zero major adverse cardiac event (MACE) rate at a median of 131 days in 10 patients treated with a paclitaxel coated Taxus DES for ISR within a sirolimus coated Cypher DES. However, this strategy may fail to prevent recurrent ISR. A 40 year old ex-smoking white female with type 1 diabetes, renal failure, hypertension, hypercholesterolaemia, and a strong family history of premature coronary disease had inferior ischaemia on a myocardial perfusion scan and a 90% stenosis in the right coronary artery at angiography (panel A). This was predilated and stented with a 2.75 × 33 mm Cypher (panel B). Secondary prevention was optimised. Six months later angiography revealed ISR within the Cypher (panel C). This was predilated with a cutting balloon and stented with a 3.0 by 28 mm Taxus (panel D). Check angiography at eight months revealed very tight ISR in the Taxus (panel E). The implantation of a Taxus stent to treat ISR within a Cypher failed to prevent recurrent ISR.