Abstract This is a randomized, phase 3 clinical trial comparing ’head to head’ nilotinib versus dasatinib as upfront therapy for patient with chronic myeloid leukemia. The efficacy of both drugs will be tested by measuring BCR/ABL using European LeukemiaNet recommendations. The study will be conducted in the National Center for Cancer Care & Research (NCCCR). Adult patients will be eligible within 6 months after the diagnosis of Philadelphia chromosome positive Chronic Myeloid Leukemia in the chronic phase. Diagnosis will be determined by conventional cytogenetic analysis of bone marrow containing at least 1 Philadelphia chromosome–positive metaphase cell. The definition of chronic-phase Chronic Myeloid Leukemia as per WHO 2016. Patients will be recruited from hematology outpatient department or in-patient wards after confirmation of the diagnosis; vulnerable subjects will be excluded from the study. The primary efficacy end point will be the rate of major molecular response at 12 months, defined as a BCR-ABL transcript level of 0.1% or less in peripheral blood on RQ-PCR assay, as expressed on the International Scale. This corresponds to a reduction of 3 log10 copies or more in BCR-ABL transcripts, as compared with the standardized baseline established in IRIS. The key secondary end point will be a durable major molecular response by 24 months. Furthermore, for this study, the rate of complete cytogenetic response by 12 months will be the main secondary end point. This trial is registered in ClinicalTrials.gov with number NCT03079505. Protocol version: August 2017