Nilotinib is an effective first-line treatment for newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase. It is an aminopyrimidine-based, high-affinity inhibitor of the tyrosine kinase activity of BCR-ABL. It thus decreases ABL-associated cell proliferation and kinase autophosphorylation. At 12 months, a significantly greater proportion of nilotinib 300 mg twice daily recipients experienced a major molecular response (primary endpoint) than those receiving imatinib 400 mg once daily, in the randomized, open-label, multicentre ENESTnd study in adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. Moreover, a significantly greater proportion of nilotinib 300 mg twice daily than imatinib recipients had a complete molecular response at 12 months. Complete cytogenetic response rates were also significantly higher in the nilotinib 300 mg twice daily group than in the imatinib group at 12 months. Treatment differences in molecular response rates remained significant in an updated analysis, with data from a minimum follow-up of 24 months. Nilotinib 300 mg twice daily was generally well tolerated in the ENESTnd study. While nilotinib is associated with an increase in corrected QT interval (QTc), the incidence of cardiac-related adverse events in nilotinib recipients in the ENESTnd study was low.