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 treatment-naive patients and healthy subjects. Method: This 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 treatment- naive 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, HBs Ab 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.