Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of blood stem cells. After the introduction of tyrosine kinase inhibitors (TKi), patients with CML have had substantially improved responses compared with previous therapies. We sought to summarize the evidence of TKi efficacy and safety in patients with newly diagnosed CML in chronic phase (CML-CP). Methods: We included all randomized clinical trials evaluating first-line treatment with a TKi (imatinib, dasatinib, bosutinib or nilotinib) in adults with CML-CP. Staudies of patients with accelerated- or blast-phase CML as well as those on IFN-α or stem cell transplantation were excluded. Main outcomes are complete cytogenetic response (CCyR) and major molecular response (MMR) at 12-month follow-up period. Safety and tolerability outcomes were pooled. A comprehensive literature search was conducted. Bayesian mixed-treatment method was used to rank TKi in terms of effectiveness. Results: Eighteen peer reviewed papers and conference abstracts reporting on seven studies were identified involving 2842 patients with CML-CP who were enrolled for initial treatment. At 12-month follow-up, mixed treatment comparison analysis demonstrated superiority of each TKi treatment family over imatinib, except bosutinib and nilotinib, which were not statistically different for CCyR and MMR respectively. Nilotinib ranked first among other TKi in terms of efficacy for CCyR; dasatinib ranked first in terms of MMR. Among second generation TKi, nilotinib had the superior tolerance and the least discontinuation rate from drug-related toxicity, followed by dasatinib then bosutinib. Hematological adverse events were highest for high dose imatinib followed by dasatinib. Conclusions: Second generation TKi are associated with a deeper and faster CCyR and MMR compared to imatinib. At 12-month follow-up period, nilotinib ranked first to achieve CCyR and had the lowest treatment discontinuation rate, while dasatinib ranked first to achieve MMR. Long term follow up is required to determine the impact of difference in the response patterns to the overall survival.