Aim: To study the comparative molecular interactions of Vinblastine and Imatinib with the active sites of Breakpoint Cluster Region (BCR)-Abelson (ABL) fusion protein using molecular docking analysis for the selective anti-Chronic myeloid leukemia (CML) activity. Materials and Methods: In this study, the binding affinity and the type of molecular interaction between the Vinblastine and the active site amino acid residues of BCR-ABL fusion protein was studied in comparison with known BCR-ABL inhibitor Imatinib. The sample size was calculated by keeping pretest G power 80%. The sample size per group is 10 (N=10) and total sample size is 20. The protein structure of BCR-ABL fusion protein was collected from the protein data bank (PDB) website and the ligand structures were collected from the NCBI-PUBCHEM website. The binding energy (kcal/mol) was calculated using Autodock Vina Software. The non-covalent protein ligand interactions were detected using protein–ligand interaction profiler (PLIP) webserver. Results: The mean binding affinity of Imatinib (-10.36 kcal/mol) was significantly (p=0.000, p<0.001, 2-tailed t-test) higher than Vinblastine (-8.72 kcal/mol) towards the active sites of BCR-ABL fusion protein. Conclusion: Though the binding affinity of Vinblastine was significantly less compared to Imatinib, Vinblastine can make strong hydrogen bonds and hydrophobic interactions with the aminoacid residues at the active sites of BCR-ABL fusion protein. It suggests that, Vinblastine may bind selectively to the cells of CML and inhibit their proliferation and can act as a novel Anti-CML agent.