Purpose: TDF is a nucleotide analogue that inhibits viral replication by direct binding to HBV RT resulting in chain termination. TDF has been approved recently in the European Union, Australia, New Zealand and Turkey for the treatment of chronic hepatitis B (CHB) in adults with compensated liver function. However clinical trials with TDF in DLD are ongoing. Methods: In 4 centers in France, data were retrospectively collected for all CHB patients treated with TDF (300 md qd) for more than 6 months and DLD, defined as Child-Pugh-Turcott score (CPT) >6, between 2002 and 2006. Results: 46 patients were identified, of whom 38 were not included in the analysis due to exclusion criteria [i.e. CPT ≤ 6 (N = 18), TDF treatment <6 months (N = 6), co-infection with HDV (N = 2), alcohol-induced cirrhosis (N = 2), Hepatocellular Carcinoma (HCC) before TDF initiation (N = 1), missing or incomplete medical files (N = 9)]. The remaining 8 patients [age: 38–49 years, males, HIV/HBV co-infected, stages CDC: 6 A and B, treated with HAART] received TDF for a median [range] duration of 47 [23–56] months. At baseline median [range] CPT score was 8.5 [7–12]. Prior to TDF treatment, 5/6 patients had HBV DNA > 400 copies/ml, and 4/6 patients had serum creatinine below the upper limit of normal at 0.9 mg/dL. Data were missing for the other 2 patients. All patients were also treated with lamivudine or emtricitabine. No death was reported for the 8 patients during the study period. Among the 5 patients who were on the liver transplant waiting list, 3 were successfully transplanted during TDF treatment. HCC was diagnosed in one patient who was subsequently transplanted with success. No hepatorenal syndrome, spontaneous bacterial peritonitis, gastric/esophageal variceal bleeding, were reported during TDF therapy. After 6 months of TDF, CPT was improved by 1 point in 2 patients and by 3 points in another patient and 3/5 patients had HBV DNA < 400 copies/ml. A transient mild increase in serum creatinine (≥0.5 mg/dL) was reported in 1 patient at 9 months and was resolved with maintenance of TDF at same dose. TDF therapy was discontinued in 3/8 patients: lack of efficacy (HBV DNA > 400 copies/mL, at 27 months (N = 1), investigator's decision (N = 1), and nephropathy possibly TDF related, that resolved after TDF discontinuation (N = 1). For this patient, serum creatinine pre-TDF was 0.7 mg/dL, and concomitant drugs included lamivudine, ritonavir and didanosine. As of December 31th, 2006, 5/8 patients were still treated with TDF. Conclusion: In this small cohort of decompensated cirrhosis in the context of HBV/HIV co-infection, TDF appeared to be effective and well tolerated. Larger prospective studies are needed to document the safety and efficacy of TDF in patients with HBV-related DLD.