Background: In spite of progress in management of high-grade Non-Hodgkin's Lymphoma (NHL), more than 30% will ultimately relapse after standard treatment. Aim of study: was to estimate early complete response (CR) as a prognostic factor for final outcome and benefit of early switching to second line chemotherapy for slow responders. Patients and Method: Newly diagnosed patients with high-grade NHL were randomized to either Group A or Group B. All patients received 3 cycles of CHOP/RCHOP while, only patients in the group B who didn't achieve early CR were shifted to second line chemotherapy. Results: The clinicopathological characteristics of patients included in the two groups were comparable. Assessment of treatment results after the 6^th cycle showed that 10 patients achieved late CR, 4 patients in group A (40%-4/10) and 6 patients in group B (6/7–85.7%). This difference was statistically significant (p-value 0.04). Out of the early CR group (24 patients), one patient died and another developed CNS relapse thus, both mortality (1/24) and relapse rate (1/23) of early CR group is 4%. Two patients of late CR group relapse (2/10-20%). The difference between the relapse rates of early CR (4%) and late CR (20%) wasn't statistically significant. The remaining 22 patients (22/23-95.7%) achieved early CR and 8 achieved late CR (8/10-80%) were in maintained remission. Regarding toxicity profile, there was no significant difference between both groups. Conclusion: Early shifting to second-line chemotherapy is tolerable and promising. However, studies with larger number of patients are mandatory to identify who may need this approach.