Data are sparse on long-term renal toxicity of tenofovir as measured by estimated glomerular filtration rate (eGFR) and progression to advanced stages of chronic kidney disease (CKD). The objective of the study is to determine the incidence of renal impairment associated with the use of tenofovir in HIV-infected patients, using abacavir as a control. In a single tertiary care center, all HIV-infected patients with baseline CKD stage 0 or 1 (CKD-1), who were started on either tenofovir or abacavir from 1998 to 2008 and had at least 1 follow-up eGFR measure on therapy, were included in this retrospective analysis. Progression to CKD stages 2 to 5 was compared using Kaplan-Meier analysis. Progression to CKD-2 and CKD-3 occurred more frequently in patients who received tenofovir than those receiving abacavir (CKD-2, 2-year actuarial frequency, 48.8% vs 23.7%; P < .001, log rank; CKD-3, 5.8% vs 0.0%; P = .028). Only 1 patient in the tenofovir group progressed to CKD-4 and none to CKD-5. Treatment with tenofovir was the only independent factor associated with progression to CKD-2 (hazard ratio [HR], 2.12; 95% confidence interval [CI]: 1.41-3.18; P < .001) and to CKD-3 (HR, 4.91; 95% CI, 1.02-23.7; P = .048). In HIV-infected patients, long-term therapy with tenofovir is associated with mild-to-moderate nephrotoxicity which is significantly higher than in abacavir-treated patients.