Inclusion Criteria: * Males ≥ 18 years of age with established severe HB (FIX:C\<1u/dl), * Treated/exposed to FIX products (e.g., concentrates or fresh frozen plasma) for at least 10 years or 50 exposure days. * A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes * Able to give informed consent and comply with requirements of the trial * Currently free of inhibitor and have no history of inhibitors to FIX protein * A negative family history for the development of an inhibitor, * Willing to practice a reliable barrier method of contraception until 3 sequential samples are negative for vector genomes using our PCR assay. Exclusion Criteria: * Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or NCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required. * Exposure to Hepatitis B or C who are currently on antiviral therapy. * Serological evidence of HTLV or active HIV infection. Individuals who are effectively being treated with antiretroviral therapy are eligible. Specific criteria for effectiveness of treatment include the following: * Documented CD4+ T-cell count of \> 350 cells/mm\^3. * HIV-1 RNA viral load \< 400 copy/ml for at least the past 12 months, including at least 2 viral load test results of \< 400 copy/ml during the immediate 12 month interval prior to screening. * Screening HIV-RNA viral load \< 400 copies/ml. * Stable HAART regimen (drugs of at least 2 different classes) for at least 12 months prior to study entry. Treatment regimen changes for dosing convenience and in response to toxicity are permitted. * Documented and confirmed (repeated) viral loads of ≥ 400 copies/ml during the 12 month time interval prior to screening are bases for exclusion although a single, unconfirmed, "glimpse" of ≥ 400 copies/ml are permitted. * Significant liver dysfunction as defined by an abnormal ALT (alanine transaminase), bilirubin, alkaline phosphatase or INR. Potential participants who have had a liver biopsy in the past 3 years will be excluded if they have significant fibrosis of 3 or 4 as rated on a scale of 0-4. * Coronary artery disease as a co-morbid condition * Platelet count of \<50 x 10\^9/l * Creatinine ≥ 1.5 mg/dl * Hypertension with systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg * History of active tuberculosis, fungal disease or other chronic infection * History of chronic disease that would adversely affect performance other than hemophilic arthropathy * Detectable antibodies reactive with AAV8 * Subjects who are unwilling to provide the required semen samples * Poor performance status (WHO performance status score \>1) or * Received an AAV vector or any other gene transfer agent in the previous 6 months * Presence of lung nodule(s) suspicious of malignancy on screening chest tomography * Presence of liver abnormalities suspicious of malignancy on screening liver ultrasound