<jats:p>A prospective multicenter Phase <jats:styled-content style="fixed-case">II</jats:styled-content> study was performed to examine the efficacy and safety of imatinib therapy in newly diagnosed Japanese patients with chronic‐phase <jats:styled-content style="fixed-case">CML</jats:styled-content>. Patients were scheduled to receive imatinib 400 mg daily. Plasma imatinib concentrations were measured by liquid chromatography–tandem mass spectrometry. In 481 evaluable patients, estimated 7‐year overall survival (<jats:styled-content style="fixed-case">OS</jats:styled-content>) and event‐free survival (<jats:styled-content style="fixed-case">EFS</jats:styled-content>) at a median follow‐up of 65 months were 93% and 87%, respectively. Because imatinib dosage was reduced in many patients due mainly to adverse events, subgroup analysis was performed according to the mean daily dose during the first 24 months of treatment: ≥360 mg (400‐mg group; <jats:italic>n</jats:italic> = 294), 270–359 mg (300‐mg group; <jats:italic>n</jats:italic> = 90) and <270 mg (200‐mg group; <jats:italic>n</jats:italic> = 67). There were no significant differences in <jats:styled-content style="fixed-case">OS</jats:styled-content> and <jats:styled-content style="fixed-case">EFS</jats:styled-content> between the 300‐ and 400‐mg groups; however, cumulative rates of complete cytogenetic and major molecular responses differed significantly between the two groups. There were no significant differences in mean imatinib trough levels between these two groups for the patients in whom trough levels had been measured. Survival and efficacy in the 200‐mg group were markedly inferior to the former two groups. These results suggest that, although a daily dose of 400 mg imatinib is associated with better outcomes, 300 mg imatinib may be adequate for a considerable number of Japanese patients who are intolerant to 400 mg imatinib. Blood level monitoring would be useful to determine the optimal dose of imatinib. (<jats:italic>Cancer Sci</jats:italic> 2012; 103: 1071–1078)</jats:p>