Hepatitis C is a blood-borne infectious disease of liver, caused by a small enveloped, positive-single strandedRNA virus, called the hepatitis C virus (HCV). HCV belongs to the Flaviviridae family and has 6 genotypesand more than 100 subtypes. It is estimated that 185 million people are infected with HCV worldwide and 5%of these are in Pakistan. The study was designed to evaluate different genotypes of HCV circulating in DistrictMardan and to know about the behavior of these genotypes to different anti-viral regimes. In this study 3,800patients were exposed to interferon alfa-2a plus Ribavirin treatment for 6-months and subjected to real-timePCR to check the viral response. Among these 3,677 (97%) patients showed no detectable HCV RNA while 123(3%) patients (non-responders) remained positive for HCV RNA. Genotypes of their analyzed showed thatmost of them belonged to the 3a genotype. Non-responders (123) and relapsed (5) patients were subjected toPEG-interferon and Ribavirin therapy for next 6 months, which resulted into elimination of HCV RNA from110 patients. The genotypes of the persisting resistant samples to anti-viral treatment were 3b, 2a, 1a and 1b.Furthermore, viral RNA from 6 patients remained un-typed while 4 patients showed mixed infections. HCV wasfound more resistant to antiviral therapy in females as compared to mals. The age group 36-45 in both femalesand males was found most affected by infection. In general 3a is the most prevalent genotype circulating indistrict Mardan and the best anti-viral therapy is PEG-interferon plus Ribavirin but it is common practice thatdue to the high cost patients receive interferon alfa-2a plus Ribavirin with consequent resistance in 3% patientsgiven this treatment regime.