This study aims to find the frequency of mutations occurring in the P-loop at three codons, 255 (E255V/K), 253 (Y253H), and 351 (M351T), in Sudanese CML patients. A hospital-based, cross-sectional, descriptive study was conducted on 99 CML patients, in 2018/05 - 2019/05. All were tested for BCR-ABL tyrosine kinase domain mutations using Nested PCR, followed by restriction enzyme digestion. Females had a higher frequency of the Y253H mutant allele over males (83.3% vs 16.7%), while males had a higher frequency of the M351T mutant allele (66.7% vs 33.3%), however, all these findings were statistically insignificant (p=0.158 and 0.258 respectively). On the other hand, the E255K mutation was distributed in 50% of each. Regarding clinical status, the mutant allele of Y253H was found in 3 out of 41 cases (6.1%) of patients undergoing Imatinib Mesylate treatment and in 3 out of 25 cases (12%) of treatment-resistant patients, but this was not significant (p=0.389). Similar results were observed for the M351T mutation, in which the mutant allele was only insignificantly higher in resistant patients than treated (p=0.22). The E255K mutant allele was detected only in patients with resistance. The T315I mutation is commoner in males, but Y253H in females, despite all mutant cases of E255K being TKI resistant and equal between sexes, with an even lower prevalence. The E255K mutation may play a larger role in TKI resistance aetiology than Y253H and M351T.