Background and Study Aims : To evaluate the effectiveness of pegylated interferon in patients with chronic hepatitis B infection in a real life setting. Patients and Methods : Fifteen hospitals in Tunisia were included in this study. Data from consecutively treated chronic hepatitis B (CHB) patients, who received pegylated interferon, were collected retrospectively. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Sustained virologic response (SVR) is defined as an hepatitis B virus (HBV) DNA concentration of less than 2,000 IU/mL six months after the completion of therapy. Results : A total of 351 CHB patients under peg interferon alfa-2a treatment were included in this multicenter, open label, non-interventional study. Thirty five HBeAg positive patients were identified (62% male, 23% advanced fibrosis). Six months after therapy, 24% had viral loads < 2000 IU/mL, 20% achieved HBeAg seroconversion and 5, 7% achieved HBs Ag loss. Three hundreds sixteen HBeAg negative patients were treated (72, 5% male, 24% advanced fibrosis). Six months post-treatment, 14 % had viral loads < 2000 IU/mL and 1, 2% achieved HBs Ag loss. Treatment was well tolerated in 92% of cases and was stopped in 5.2% of patients. In multivariate analysis, predictors of response to pegylated interferon were: age less than 50 years (P=0,04 IC [0,169-0,737]), precore mutant stain infection (p=0,04 IC [0,60-0,69]), a body mass index < 30kg/m 2 (P=0,05 IC [0,225-0,320]), and a pre-treatment serum HBV DNA level <20000IU/ml (P=0,03 IC [1,316-2,225]). Conclusion : PEG-IFN therapy in chronic hepatitis B (CHB) is well tolerated and can achieve a good response especially if we select good responders.