The objective of this study was to analyze the use of sirolimus-eluting stent (SES) placement for the treatment of renal artery in-stent restenosis (RA-ISR). The optimal treatment of RA-ISR has not been fully elucidated to date. We retrospectively analyzed consecutive patients from our institution who underwent treatment of RA-ISR with a SES from May 2004 to June 2006. Using duplex ultrasound, RA-ISR (> 60% diameter) was determined by peak systolic velocity (PSV) > 300 cm/s and renal aortic ratio (RAR) > 4.0. Renal function (creatinine) and blood pressure were measured at baseline and follow-up. SESs were implanted in 16 patients (22 renal arteries) during the study period. The study cohort was predominantly female (75%) with a mean age of 68 +/- 12 years. RA-ISR was treated with SESs with a mean diameter of 3.5 mm and mean length of 17.9 +/- 3.8 mm. The mean post-dilation balloon diameter was 4.8 +/- 0.6. The baseline renal artery PSV was 445 +/- 131 cm/s with a mean RAR of 5.0 +/- 1.6. Follow-up information was available in 21 renal arteries. During a median follow-up of 12 months (range: 9-15 months), 15 renal arteries (71.4%) developed recurrence of ISR by ultrasonographic criteria. Univariate analysis revealed that female sex was an independent predictor of recurrence of ISR after SES implantation (p < 0.05). In conclusion, placement of a SES for the treatment of ISR in renal arteries is associated with high initial technical success but significant restenosis on duplex ultrasonography at follow-up.