Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that originates in an abnormal pluripotent bone marrow stem cell and is constantly associated with BCR-ABL fusion gene. The present study was undertaken to obtain the clinical and hematological profile in adult CML patient. An attempt had been made to evaluate as well as compare the response of patients to the drugs - Hydroxyurea and Imatinib Mesylate. The earlier is an S phase acting agent and acts by inhibiting DNA synthesis while the latter is a potent and selective tyrosine kinase inhibitor. Methods: This was a prospective study done between January 2000 to march 2011 in department of pathology and medicine at Banaras Hindu University. A total 50 patients were studied. Exclusion criteria- pregnant ladies and children below 16 years were not included in the study. Patients on hydroxyurea were given 1000mg/day in chronic phases while those in accelerated phase and blast crisis received 30000 mg daily. The patients in imatinib mesylate group in chronic phase received single dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Complete blood counts were monitored weekly for the first month, fortnightly thereafter till patient achieved hematological remission and then monthly. Interchange of patients among the groups was allowed. The diagnosis was based on general blood picture and bone marrow aspiration was ever needed. The standard criteria for the diagnoses of chronic phase, accelerated phase and blast crisis were used. Results: Chronic myeloid leukemia was commoner in males (male to female ratio was 1.4. Both the drugs were not age and gender sensitive. There was no significant difference in Imatinib and hydroxyurea group in mean post treatment TLC, mean post-treatment PLT, mean post-treatment HB, and mean post treatment spleen levels of patient according to the criteria of phases of disease though side effects were significantly lower with imatinib. Imatinib mesylate, a selective inhibitor of the protein tyrosine kinase has shown promising results in chronic myeloid leukaemia in all phases. Its efficacy, specificity and the safety profile makes it a better choice for the first line therapy in CML.