Purpose: The effective treatment of chronic myeloid leukemia (CML) remains a challenge due to non-adherence to Imatinib. We aimed to assess the factors associated with non-adherence to Imatinib therapy in newly diagnosed patients with CML. Methods: Eighty-two adult patients initiating Imatinib were recruited. Adherence was measured using medication possession ratio (MPR) and visual analogue scale (VAS) at 90 days. Demographic, clinical and quality-of-life variables were assessed at baseline. Pearson’s correlation and linear regression analyses were performed to identify associations and independent predictors of non-adherence respectively. Results: Twenty-two percent (18/82) of patients were non-adherent (MPR ≤ 85). Self-reported adherence via VAS correlated significantly with MPR. Among various factors, cognitive function score and occurrence of adverse drug event (ADR) were associated with adherence. The impact of disease on daily-life score was negatively associated with adherence. The independent predictors of adherence were role function score and impact of disease on mood score. Conclusions: This study identified cognitive and role function, impact of disease on daily life and mood and occurrence of ADR as variables influencing non-adherence to Imatinib in CML patients. Early identification of these factors can guide interventions to improve adherence and treatment outcomes.