Objective:To evaluate the efficacy and safety of nilotinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP). Methods: A total of 65 CML-CP patients received nilotinib 600~800 mg orally twice daily or imatinib 400 mg orally once daily. Data on curative efficacy and tolerance were collected and compared. Results:Of 65 CML-CP patients, 26 patients received nilotinib and 39 received imatinib. The both median duration of therapy and follow-up were 19.5 (5~39) months. ①The rates of major molecular response (MMR) at 3,6,12 months were higher in nilotinib group than those in imatinib group(23.1% vs. 7.6%, 45.5% vs. 22.2%, 66.7% vs. 54.8%, respectively). There was significantly statistic significance between two groups at 6 months. MMR rates by 12 months in low, intermediate and high sokal risk groups on nilotinib and imatinib were 81.3% vs. 42.8%,42.8% vs. 57.1%,66.7% vs. 50%, respectively. The rates of Bcr-Abl ≤ 10% at 3 months, <1% at 6 months and <0.1% at 12 months were higer in the nilotinib group than those in the imatinib group (80.8% vs. 41%, P=0.002, 77.3% vs. 48.5%,P=0.033 and 66.7% vs. 54.8%, P=0.394). The median time to MMR was significantly shorter for nilotinib than that for imatinib (14 months vs 34 months). The rate of complete cytogenetic response (CCyR) at 3, 6 and 12 months in the nilotinib and the imatinib group were 76.9% vs. 52.9%, 89.5% vs. 70% and 78.5% vs. 77.3%, respectively. The median time to CCyR was 3 months in imatinib group and 6 months in nilotinib group. ② The drug related adverse events were mostly grade 1/2 and were well tolerated by most of the patients. Conclusion:Nilotinib can reach molecular response in a shorter time than imatinib and also has a confirmed efficacy and tolerability in newly diagnosed CML-CP patients and can be used as first-line therapy.