Background: In 2013 ELN proposed new response categories applicable to TKI frontline therapy for CML. We analyzed the outcome by ELN category of patients (pts) on different TKI as frontline therapy for CML-CP. Methods: 487 pts treated by TKI from 2000-2013 were analyzed. Pts received imatinib 400 mg/d (IM400; n=70), imatinib 800 mg/d (IM800; n=201), dasatinib (n=107) or nilotinib (n=109) in consecutive or parallel trials. Median follow-up was 99 months (mo). Pts were followed uniformly with cytogenetics and PCR every 3 mo for the first 12 mo, then every 6 mo. Results: Median follow-up was 144 mo for IM400, 119 mo for IM800, 54 mo for dasatinib and 49 mo for nilotinib. Cumulative CCyR rates were 85%, 90%, 98% and 93%, and MMR rates were 84%, 88%, 91%, and 94%, respectively. ITT analysis indicated the proportion of pts falling into optimal, warning and failure categories were 89%, 6%, 6% at 3 mo, 78%, 17% and 6% at 6 mo, and at 12 mo 75%, 13% and 13%, respectively. Rates of optimal response at 3 mo were 75% for IM400, 90% for IM800, 89% for dasatinib and 97% for nilotinib; 41%, 80%, 86% and 89% at 6 mo; and 47%, 77%, 76% and 87% at 12 mo, respectively. Pts with optimal response had longer EFS, FFS, TFS and OS compared to those with warning and failure at all-time points. Within each response category, type of TKI did not affect long-term outcome. (Table) Conclusions: Imatinib 400 induces optimal response in fewer pts at all times. Optimal responses predict for better outcomes irrespective of the TKI modality.