Tyrosine kinase inhibitor like Imatinib, a small-molecule drug, targets and inhibits the BCR-ABL tyrosine kinase by competitive binding at the ATP-binding site.If Imatinib treatment fails, mutational analysis could identify highly resistant mutants of the kinase domain. Materials and Methods: A retrospective observational study was conducted in a tertiary care institute to evaluate response of Tyrokinse inhibitors after 18 months of treatment. Results Most of the patients amongst the cohort of 30 had a favourable response to Imatinib at the end of 18 months.Four patients had response failure due to either mutation or high EUTOS score. However long term survival had increased in almost all patients. Conclusions: Primary end point of regression of splenomegaly and hematological response was achieved within first three months in all except 3patients. cytogenic and molecular response was achieved in all except 4 patients at the end of 18months. Mutations were observed in only 2 cases.Survival benefit was present in all.