180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 &36 for therapeutic success evaluation. A significant reduction in Hb levels (p<0.05) was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm(3). End Treatment Response (ETR) was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age.