Background: Chronic hepatitis C (CHC) is an important liver disease, which may progress to cirrhosis or hepatocellular carcinoma. The current treatment regimen for CHC includes pegylated interferon-α (PEG-IFN) combined with ribavirin Ferritin is the major iron storage protein and provides an indirect estimate of the body's iron stores. It is also an established marker for liver iron deposition. Aim of the Work: The aim of this study is to configurate the distribution of iron and ferritin levels in patients with chronic hepatitis C virus infection and to conduct a comparative study between the pretreatment and the post treatment iron profile after direct acting antiviral therapies in chronic HCV patients. Patients and Methods: This Randomized Controlled Clinical study was conducted on 100 subjects aged from 18 to 60 years selected from Gastroenterology and Hepatology department at Ain Shams University Hospital, Cairo, Egypt, from January 2017 to April 2017 and was approved by the ethical committee. Results: The current study suggests that a 12 weeks course of Sofosbuvir / Ledipasvir combination drug therapies showed a higher SVR 12 (92 %) and have significant decrease of the elevated serum iron and ferritin and transferrin saturation to the normal level more than sofosbuvir / Daclatasvir which showed a SVR 12 (88%). In both study groups, patients who showed SVR had significant lower values of Iron, Ferritin and transferrin saturation levels than patients who were non-SVR after end of therapy. Conclusion: This study may also shed light on how the changes in serum iron and ferritin levels in chronic hepatitis C patients may be related to HCV treatment. Recommendations: Sofosbuvir / Ledipasvir 12-weeks course is more recommended than Sofosbuvir / Daclatasvir 12 weeks course in patients with chronic HCV infection. As serum Iron, serum Ferritin and Transferrin saturation showed more significant improvement with SOF/LED combination therapy than SOF/DAC combination therapy, they are a good markers of highly predictive value in treatment of chronic HCV infected patients with DAAs.