Patients undergoing chronic hemodialysis (HD) are at high risk of restenosis and cardiac events after percutaneous coronary intervention (PCI). This study compared the clinical efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients undergoing HD. Between June 2004 and January 2010, the clinical outcomes of 41 consecutive patients on HD who underwent PCI with SES (62 lesions) were compared with those of 38 consecutive patients on HD who underwent PCI with PES (54 lesions). Patient and lesion characteristics were similar between both groups. The target lesion revascularization (TLR) (SES 36.6 % vs. PES 15.8 %; P = 0.037) was significantly higher with SES (36.6 %) than with PES (15.8 %) (P = 0.037), particularly in the context of severe calcified lesions that required rotational atherectomy (SES 72.7 % vs. PES 16.7 %; P = 0.0067). However, 1 year after PCI, there was no difference between the two groups in all-cause death, myocardial infarction or major adverse cardiac events. Patients undergoing HD are at a high risk of restenosis after PCI, even when using a drug-eluting stent. The TLR was higher with SES than with PES, particularly when used for severe calcified lesions that required rotational atherectomy.