A 36 year old man with chronic hepatitis B and cirrhosis was admitted in our Department for the onset of jaundice, ascites and ALT flare (x 35 u.n.v.) while under lamivudine treatment. Serum HBV-DNA was 1.48 x 10(6) IU/ml and lamivudine (LAM) resistance mutations were present. Tenofovir (TDF) 300 mg/day was added to LAM after its off-label use was authorised. HBV-DNA decreased in a biphasic manner and became undetectable by day 45. A parallel improvement in ALT and bilirubin values was detected. Tenofovir was substituted with adefovir dipivoxil 10 mg/day. Ten months after this switch HBV-DNA remained undetectable. Tenofovir is an effective salvage therapy for critically ill patients with LAM-resistant HBV flares and can be switched to adefovir after HBV-DNA becomes undetectable. Local cost and reimbursement policies are important determinants in antiviral therapy.