© 2017 Elsevier Inc.Micro-Abstract We retrospectively evaluated 90 patients with chronic myeloid leukemia receiving either upfront original imatinib (OI) or generic imatinib (GI) for the effect of the early molecular response on the long-term outcome. We demonstrated that achieving an optimal response at 3 and 6 months in patients receiving either first-line GI or OI was clearly associated with greater response and event-free survival rates. Background The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). Patients and Methods We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). Results Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P =.553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. Conclusion The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.