Background: A diverse category of malignant lymphocyte neoplasms, lymphomas may affect extra nodal locations, bone marrow, or lymphatic tissue. This study aimed to determine the lymphoma patients' red cell distribution width (RDW) and how it relates to their prognosis. Methods: One hundred lymphoma patients who visited Benha University hospitals for follow-up were included in this prospective cohort research. There were two groups of patients: Group A: 77 patients who responded fully to therapy. Group B: 23 patients who responded partially or refractorily to therapy. Results: The international prognostic index (IPI) and RDW were shown to be independent predictors of partial/refractory therapy response by the multivariate analysis. High stage lymphoma, extra nodal lymphoma, B symptoms, lactate dehydrogenase level, and bone marrow involvement were all significant predictors of partial/refractory treatment response, according to the univariate analysis. A 75.6% higher chance of a partial or refractory treatment response was linked to a one unit rise in RDW in the multivariate. Conclusion: For instances of lymphoma, RDW and IPI are independent, significant predictors of partial or refractory response. Analysis of the receiver operating characteristics curve was done for RDW in order to forecast the response to partial or refractory therapy. With a 95% CI between 0.620 and 0.899 and a large area under the curve of 0.760, the results indicate a decent capacity to predict partial or refractory treatment response. Sensitivity, specificity, positive predictive value, and negative predictive value were 69.57%, 92.21%, 72.7%, and 91%, respectively, at the optimal cutoff of >15.8%.