Orally administered angiotensin receptor antagonists administered after bare-metal stent implantation and even after drug-eluting stent implantation seem to lower in-stent restenosis rates.Whether valsartan-eluting stents are similarly effective was tested here in a first-in-man trial. The efficacy of a polymer-free drug-eluting stent coated with 300 mcg valsartan was compared to a coating with a 2% rapamycin solution in small (<or= 2.5 mm) coronary vessels with and without oral valsartan on the basis of the YUKON Choice stent system (Translumina GmbH, Hechingen, Germany). Fifteen patients (eight males, mean age 64.4+/-7.7 years) were treated with YUKON Choice valsartan-eluting stents and 30 patients (24 males, mean age 65.7+/-8.4 years) received YUKON Choice rapamycin-eluting stents. Clopidogrel was given for six months in all patients. Within the first 30 days, no adverse events occurred in either group. Binary in-stent restenosis rate was 30.8% (four in 13 angiographic controls) in the valsartan-eluting stent group and 35.0% (eight in 20 angiographic controls) in the rapamycin-eluting YUKON Choice stent group. Mean late lumen loss was 0.78+/-0.53 mm and 0.79+/-0.58 mm, respectively. Target lesion and target vessel revascularisation rate was 26.6% and 25.0%, respectively. No restenoses in rapamycin-eluting YUKON Choice stents appeared in 12 patients with adjunct oral valsartan administration. If polymer-free YUKON Choice stents are used in small vessels, valsartan-eluting stents show an identical efficacy as rapamycin-loaded stents. In patients with rapamycin-eluting YUKON Choice stents it seems that the efficacy can be increased by oral valsartan administration.