The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a major public health problem in Egypt. The objective of this study was to detect the clearance of HCV-RNA in Egyptian patients who were recommended for combination therapy of pyglated interferon α 2a and ribavirin (PEG-interferon/Ribavirin). Ninety-five positive HCV-IgG cases were tested for HCV-RNA at baseline and at weeks 4, 12, 24, 48 and 72 of treatment with PEG-interferon α 2a/Ribavirin. The correlations between the viral parameters during and after treatment were evaluated. Patients recommended receiving PEG-interferon 2a/ribavirin combination therapy showed high response rate determined as 71.9% achieved Sustained Virological Response (SVR) from total patients, and 71.4% from patients who received 48 weeks therapy. In general, the employment of TMA provided us the accuracy of results with confidence in our work. There was a significant relation (p < 0.001) between results of Transcription mediated amplification (TMA) and response to therapy that indicate to positive correlation. The development of sensitive accurate assays for HCV-RNA detection and quantification is necessary to improve not only the assessment of the response to antiviral therapy but also our understanding of the mechanism underlying antiviral resistance.