: Platelet function in chronic myeloid leukemia (CML) could be affected by either hyperleucocytosis, clonal megakaryopoiesis, or tyrosine kinase inhibitors. However, these variables have never been prospectively evaluated. We conducted a prospective study over a period of 1.5 years in a tertiary care center of north India. Patients with CML in chronic phase, more than 18 years, and treated with imatinib were enrolled (n = 32). Age, and sex-matched controls were also included. Platelet function test was performed using two-channel Chrono-Log aggregometer 490 at four time-points: first, at diagnosis; second, after leucoreduction (total leucocyte count, <10 × 10/l) achieved with hydroxycarbamide; third, on-imatinib at BCR-ABL less than 1%; and fourth, in an independent cohort (off-imatinib) at deep molecular response (DMR) (BCR-ABL < 0.01%). Statistical analysis was performed using IBM SPSS statistics (version 22.0). Median age of patients was 42 years (15-65), and M : F ratio was 1 : 1. At diagnosis, platelet function correlated negatively with total leucocyte count, but not with platelet count. As compared with baseline, platelet aggregation with ADP (2.5 μl), and collagen (2.5 μl) improved significantly after leucoreduction (P = 0.05 and 0.009, respectively). Imatinib further caused significant impairment of aggregation with ADP (2.5 μl), collagen (2.5 μl), and collagen (1 μl) (P = 0.04, 0.008, and 0.02, respectively). Patients in DMR also demonstrated a significant impairment of platelet aggregation with all the agonists as compared with controls. While leucoreduction alone can improve the baseline platelet function derangement in CML, imatinib further impairs it. Residual CML stem cells, or effect of imatinib on normal common myeloid progenitors might account for platelet function derangement at DMR.