Background: Rituximab is currently approved for the treatment of relapsed and refractory indolent lymphomas, which was added to the protocol in Yemen although it was highly costly. The study aimed to determine the long-term response of rituximab on Non-Hodgkin Lymphomas (NHL) patients. Methods: A retrospective cohort study was conducted in the National Oncology Center (NOC) in Aden by review of medical registries for NHL patients from 2017-2020. Sociodemographic and clinical data were extracted from patients’ files by a well-trained team. SPSS version 23 was used for the analysis of data, and Kaplan Meier survival curve was used to measure overall survival (OS) and progression-free survival (PFS) between two groups CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and rituximab-CHOP group in two follow up periods (12-months and 4-years). Cox regression was used to evaluate the association between the risk factors. A P-value of < 0.05 at a confidence interval of 95% is considered statistically significant. Results: Of 100 patients, 50 for each group of CHOP and R-CHOP. The under 60 years represented 70%. Advanced Stage represented 64% and diffuse large B cell lymphoma represented 47% of all subtypes of NHL. Significant association difference in OS in two periods of follow-up (12-month and 4-years) for CHOP vs. R-CHOP was 63% vs. 86%, and 10% vs. 33%, respectively (P=0.01 and P=0.04). In contrast, the difference was non-statically significant in the PFS in two periods 39% vs. 66%, and 12% vs. 27% for CHOP vs. R-CHOP, respectively (P=0.10 and P=0.31). The age group > 60 years, ≥ 6 cycles of chemotherapy received, abnormality of LDH, and married patients were the significantly hazard proportion that was associated with poor prognostic factors (P= 0.009, 0.001,0.010, and 0.011, respectively). Conclusion: The addition of rituximab to CHOP chemotherapy had a statistical difference in overall survival and there is no difference in PFS. Elderly, married patients, more than 6 cycles of chemotherapy received, and abnormality of LDH were the most important prognostic factors. Therefore, providing the oncology center with Rituximab for ongoing use of NHL patients especially those under 60 years, further assessment for hospital-related risk factors that lead to decreased survival are recommended.