Background: Hepatitis C virus HCV infection is one of the main causes of chronic liver disease worldwide, Egypt has the highest national-level HCV prevalence in the world, Sofosbuvir/ Daclatasvir (SOF/DAC) regimen widely used to treat HCV infection in Egypt.
 Aims: to identify the predictors of treatment failure with Sofosbuvir/Daclatasvir regimen for 12 weeks in HCV Egyptian patients.
 Methodology: A retrospective cohort, we investigated the predictors of treatment failure in 2300 HCV patients received the SOF/DAC regimen in Egypt.
 Results: Patients who completed the treatment and follow up visits were 2079 patients,4 patients stopped treatment due to side effects, 35 due to incompliance and 182 patients missed their follow up visits after treatment, out of the 2079 patients 2043 (98.3%) patients responded to treatment with SVR12 and just 36 (1.7%) patients had treatment failure, presence of Hypertension (p=0.001), Diabetes Miletus (p=0.001), ALT level >51 (p=0.013) , AST level >60 (p=0.002), AFP > 6 (p=0.000) and abnormal liver echo-pattern all were found to have an impact on SVR12 rates, some other factors were found to be insignificant as age, sex, BMI, special habits, liver function tests, haemoglobin, total leucocytic count and serum creatinine, by multivariate analysis AFP was found to be the strongest predictor of treatment failure with cut off value >6 with sensitivity 66.67% and specificity 77.31%.
 Conclusion: This study shows that ALT, AST, AFP, Abnormal Liver Echo-pattern and the Presence of Diabetes Miletus or Hypertension were found to affect SVR rates, but the strongest predictor was AFP level with a cutoff value of >6.