Background: Nilotinib and dasatinib are BCR-ABL inhibitors that markedly differ in selectivity. In separate randomized trials, nilotinib and dasatinib have shown superior achievement of molecular response (MR) compared to imatinib for the treatment of newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP). In the absence of head-to-head trials, health technology assessment authorities rely on indirect comparisons to inform drug policies. This study compares MR between nilotinib 300mg twice daily and dasatinib 100mg once daily by 12 months and through 48 months via indirect comparison. Methods: Data were drawn from individual patients in the ENESTnd trial (nilotinib vs. imatinib) and published results from the DASISION trial (dasatinib vs. imatinib). Patients in ENESTnd were re-weighted to match baseline characteristics reported for DASISION (age, sex, ECOG performance status, white cell count, and platelet count) using a propensity score model. After matching, differences in major MR (MMR measured as a 3-log reduction on the International Scale [IS]), MR^4.0 (4-log reduction on IS) and MR^4.5(4.5-log reduction on IS) rates between nilotinib and imatinib were compared with those between dasatinib and imatinib. Cumulative MR rates through 48 months were also compared using adjusted hazard ratios (HRs) relative to imatinib. Results: After matching, rates of MR by 12 months were higher with nilotinib vs. dasatinib by 11.7% for MMR (p = 0.045), 8.2% for MR^4.0 (p = 0.029), and 8.5% for MR^4.5 (p < 0.001). Through 48 months of follow-up, the adjusted HR comparing MMR achievement with nilotinib vs. dasatinib was 1.44 (95% CI: 1.06, 1.94; p=0.018); the corresponding HRs for MR^4.0 and MR^4.5were 1.58 (95% CI: 1.10, 2.26; p=0.013) and 1.30 (95% CI: 0.86, 1.99; p=0.218), respectively. Conclusions: This indirect comparison suggested that nilotinib 300mg twice daily was associated with higher rates of achieving MMR, MR^4.0, and MR^4.5 by 12 months compared to dasatinib 100mg once daily for the treatment of newly diagnosed CML-CP. Higher rates of MR achievement with nilotinib were also maintained through 48 months of follow-up.