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Renal dysfunction is a common and costly adverse outcome of long-term treatment with calcineurin inhibitors (CNIs). We conducted a retrospective, case–control study to test whether the risk of renal dysfunction in liver transplantation patients receiving CNIs is associated with the 2677G>T transversion in exon-21 of the gene (ABCB1) encoding P-glycoprotein. A total of 120 non-Hispanic white patients were evaluated.The overall incidence of renal dysfunction by year 3 post-transplantation was 40%. The frequency of renal dysfunction was reduced among patients with an ABCB1 2677TT genotype, as compared to those with a 2677GG genotype. Subjects with a heterozygote genotype behaved phenotypically like the 2677GG group. Comparing those subjects with a 2677TT genotype to the combined group of subjects with a 2677GG, TG, AT, or AG genotype resulted in an odds ratio of 0.26 (0.09–0.77). When subjects were stratified by gender, the frequency of renal dysfunction was reduced among men with an ABCB1 2677TT genotype, relative to men with different genotypes. A similar odds ratio was obtained for women, but it did not achieve significance. When 18 subjects with an elevated SCr concentration just prior to surgery were excluded from the year 3 analysis, the association between the 2677TT genotype and chronic renal dysfunction in the remaining cohort was strengthened comparing genotype groups.Based on these results, we conclude that homozygosity for the ABCB1 2677T (S893) allele is associated with reduced risk of chronic renal dysfunction among liver transplantation patients receiving an immunosuppressive regimen containing CNIs.