Background and Aims: In Egypt, compulsory vaccination against hepatitis B virus (HBV) infection started in 1992. Patients with chronic hepatitis C (CHC) should be vaccinated against HBV. The aim was to assess the response to HBV vaccine in CHC patients treated with direct acting antivirals (DDAs) in comparison to treatmentnaive patients and healthy subjects. Method: This retrospective-prospective study was carried out on 360 consecutive adult subjects subdivided into 3 groups. Group I included 150 CHC patients who vaccinated after getting sustained virologic response (SVR) following treatment with DAAs. Group II comprised 110 CHC treatmentnaive patients while the control group comprised 100 healthy subjects. Three intramuscular 20 µg doses (at 0, 1 & 6 months) of HBV-vaccine (rDNA) were administered; HBs Ab titres were evaluated 6 – 8 weeks after the 3rd dose. Results: CHC patients (treated or treatment-naïve) had highly significant lower mean HBs Ab titre than controls. Twelve patients in group I (8%) had no response to HBV vaccine in comparison to 4.5% in group II and 1% controls. About 83.3%in group I compared to 85.5% in group II and 98% controls had a good response. In CHC treated patients, HBsAb titre was negatively associated with FIB-4 score, fibrosis stage and ALT levels while positively associated with platelet count. The fibrosis stage was the most significant predictor of weak response. Conclusion: CHC Patients demonstrate a significantly weak response to HBV vaccine. Concomitant DAAs treatment does not influence response.