Abstract: End stage renal disease is a major complication after orthotopic liver transplantation (OLT). Vasoconstriction of renal arterial vessels because of calcineurin inhibitor (CNI) treatment plays a pivotal role in the development of renal insufficiency following OLT. Renal resistance can be measured non-invasively by determining the resistance index (RI) of segmental arteries by color-coded duplex ultrasonography, a measure with predictive value for future renal failure. Sixteen OLT patients on long-term CNI therapy were recruited prospectively and randomly assigned either to receive the m-TOR inhibitor sirolimus (SRL) or to continue on CNI treatment, and were followed for one yr. Serum creatinine (crea) declined after conversion to SRL, whereas it tended to increase in patients remaining on CNI (meanΔ crea SRL: −27, −18, −18, −15 μmol/L; meanΔ crea CNI: 4, 5, 8, 11 μmol/L at 1, 3, 6, 12 months, p = 0.02). RI improved after switching to SRL and was lower on SRL than on CNI (meanΔRI SRL: −0.04, −0.04, −0.03, −0.03; meanΔRI CNI: −0.006, 0.004, −0.007, −0.01 after 1, 3, 6, 12 months, p = 0.016). Individual changes of RI correlated significantly with individual changes of crea (r = 0.54, p < 0.001). Conversion from CNI to SRL can ameliorate renal function accompanied by a reduction of intrarenal RI after OLT.