Background: TKI discontinuation for CML pts may be considered for those who achieve the deepest molecular responses as qualified by MR4.5 and complete molecular response for ≥ 2 years (susMR4.5). We describe the cumulative incidence of susMR4.5, the long term impact of susMR4.5 and baseline characteristics of those pts. Methods: 522 pts treated with TKI in prospective clinical trials followed at our institution for ≥ 2 years between 2000 and 2015 were analyzed for time to susMR4.5, long term impact of susMR4.5 after achieving complete cytogenetic response for ≥ 2 years (susCCyR) as measured by event-free survival (EFS), transformation-free survival (TFS) and overall survival (OS), and their baseline characteristics. Results: Among pts analyzed, 65 (12%) were treated with Imatinib 400mg (IM400), 183 (35%) with Imatinib 800mg (IM800), 121 (23%) with Nilotinib (NILO), 113 (22%) with Dasatinib (DASA) and 40 (8%) with Ponatinib (PONA). After a median follow-up of 106.9 mo (range 17.0-177.9), 311 (60%) pts achieved susMR4.5 with a median time to susMR4.5 of 17.6 mo (range 2.7-107.8). The incidence of susMR4.5 for IM400, IM800, DASA, NILO and PONA was 25 (38%), 120 (66%), 73 (65%), 75 (62%) and 18 (45%), respectively. IM400 was statistically inferior to IM800, DASA and NILO at achieving susMR4.5 (p = < 0.001). In the 418 pts attaining susCCyR, there was no difference in EFS, TFS and OS between pts who also achieved susMR4.5 and pts with only MR4.5 (p = 0.369, p = 0.468, p = 0.129). There was improved EFS and TFS between susMR4.5 pts and pts who never reached MR4.5 (p = < 0.001, p = < 0.001) with a trend towards improved OS (p = 0.08). Older age corresponds to susMR4.5 (p = 0.003) while other baseline characteristics such as race, sex, Sokal score and initial stage at diagnosis had no correlation. Conclusions: In pts who achieve susCCyR, attaining susMR4.5 and MR4.5 had equal long term outcomes, but not achieving MR4.5 was worse for EFS and TFS with a trend towards worse OS. Attaining susMR4.5 depended on initial frontline TKI choice as higher potency TKIs (IM800, DASA and NILO) was superior to IM400. Older age was the only predictive baseline characteristic for pts achieving susMR4.5.