Imatinib mesylate (IM) is a first-line treatment of chronic phase-chronic myeloid leukemia (CP-CML). The primary objective of this study was to assess the quality of life (QOL) in patients with CP-CML treated with IM. Ninety patients with newly diagnosed CP-CML were assessed for QOL with first-line IM. Patients completed the cancer-specific FACT-BRM questionnaire (functional assessment of cancer therapy-biologic response modifiers) at baseline and at 3 and 6 months. FACT-BRM consists of subscales including physical well-being (PWB), social and family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), BRM-physical, and BRM-mental. The primary endpoint was the Trial Outcome Index (TOI), created as a measure of physical function and well-being. An increase of ≥5 from baseline was considered to be a clinically significant improvement. The mean TOI score increased from 75.5 at baseline to 85.2 (p<0.0001) at 6 months, representing a healthy QOL. When comparing the individual TOI subscales, there was a mean increase of 16.4 in the daily functioning and well-being score, and a mean decrease of 6.2, 4.9, and 16.1 was noted in fatigue, emotional/cognitive dysfunction, and side-effects scores at 6 months, respectively. Improvement was not affected by age, sex, or Sokal score. With prolonged treatment, IM results in a higher physical well-being, less fatigue and emotional and cognitive dysfunction, and very few side-effects.