This observational， prospective study assessed， in a daily clinical practice， the molecular response， safety， quality of life (QoL) and treatment adherence in 183 patients with chronic myeloid leukaemia in chronic phase (CML-CP)， receiving nilotinib as first-line treatment. Premature study termination before 24 months of follow-up occurred in 61 patients (33·3%)， and was essentially due to nilotinib treatment discontinuation (n = 53; 29%)， motivated by treatment intolerance (n = 29; 15·8%) and inefficacy (n = 19; 10·4%). After 24 months of treatment， 112/122 patients (91·8%) had a molecular assessment， 95·5% of whom achieved a major molecular response (MMR)， 32·1% achieved uMR ， defined as an undetectable molecular disease with 4-log molecular response sensitivity (≥10 000 ABL1 transcripts). The Morisky Green Levine Medication Adherence Scale was completed by 94/122 patients (77·0%)， and 89·4% of these patients obtained a satisfactory level of treatment adherence， defined as a score ≥3. Patients' QoL was good at baseline and stable during the follow-up period. The two most common nilotinib-related adverse events (AEs) were pruritus (14·8%) and asthenia (13·7%). Seven patients (3·8%) experienced at least one cardiovascular ischaemic AE. This French nationwide cohort study provides relevant information in daily clinical practice indicating that nilotinib is a valuable first-line treatment option for CML-CP patients.