The proportion of patients undergoing liver transplantation (LT) with renal insufficiency has significantly increased in the Model for End-Stage Liver Disease (MELD) era. This study was designed to determine the incidence and predictors of post-LT chronic renal failure (CRF) and its effect on patient survival in the MELD era. Outcomes of 221 adult LT recipients who had LT between February 2002 and February 2007 were reviewed retrospectively. Patients who were listed as status 1, were granted a MELD exception, or had living-donor, multiorgan LT were excluded. Renal insufficiency at LT was defined as none to mild [estimated glomerular filtration rate (GFR) ≥ 60 mL/minute], moderate (30–59 mL/minute), or severe (<30 mL/minute). Post-LT CRF was defined as an estimated GFR < 30 mL/minute persisting for 3 months, initiation of renal replacement therapy, or listing for renal transplantation. The median age was 54 years, 66% were male, 89% were Caucasian, and 43% had hepatitis C. At LT, the median MELD score was 20, and 6.3% were on renal replacement therapy. After a median follow-up of 2.6 years (range, 0.01–5.99), 31 patients developed CRF with a 5-year cumulative incidence of 22%. GFR at LT was the only independent predictor of post-LT CRF (hazard ratio = 1.33, P < 0.001). The overall post-LT patient survival was 74% at 5 years. Patients with MELD ≥ 20 at LT had a higher cumulative incidence of post-LT CRF in comparison with patients with MELD < 20 (P = 0.03). A decrease in post-LT GFR over time was the only independent predictor of survival. In conclusion, post-LT CRF is common in the MELD era with a 5-year cumulative incidence of 22%. Low GFR at LT was predictive of post-LT CRF, and a decrease in post-LT GFR over time was associated with decreased post-LT survival. Further studies of modifiable preoperative, perioperative, and postoperative factors influencing renal function are needed to improve outcomes following LT. Liver Transpl 15:1142–1148, 2009. © 2009 AASLD.