Objective: The aim of this study is to comprehensively evaluate the safety and efficacy of the 20-kDa linear (Pegylated Interferon) PEGIFN alpha-2a and Ribavirin combination versus Sofosbuvir, 20-kDa linear PEGIFN alpha-2a and Ribavirin combination in treatment of chronic hepatitis C (CHC) Egyptian patients as well as studying variables that affect the response to this treatment. Methods: A total of 202 adult Egyptian patients divided into 2 groups; IR group composed of 97 patients enrolled to receive PEG-IFN and RBV combination treatment, and IRS group composed of 105 patients enrolled to receive PEG-IFN, RBV, and sofosbuvir combination.  Results: In IR group 62 (63.92%) had end of treatment response (ETR), of the 62 patients with ETR, 11(11.34%) had a relapse while 51 (52.58%) patients achieved sustained virological response (SVR). In IRS group six (5.72%) patients were non-responders, where as 99 (94.28%) patients attained ETR of whom 29 (27.62%) had a relapse while 70 (66.67%) patients achieved SVR. Conclusion: This new combination containing sofosbuvir is still ineffective enough so that more researches and treatment combination needed to combat hepatitis C epidemic in Egypt at reasonable cost.