Objective: This study is intended to evaluate the costs derived from the treatment of aggressive and indolent Non-Hodgkin Lymphoma (NHL), in patients treated with R-CHOP vs. CHOP in order to provide solid pharmacoeconomic arguments for decision-makers in regards to a cost-effective therapy for patients with NHL and hence have a more efficient allocation of resources. Methods: A cost-effectiveness analysis model was developed based on the efficacy reports of the international literature in regards to treatment of NHL estimating the probabilities of no remission or disease relapse and the costs of treatment failure and those derived from salvage therapies used. This was calculated in a time horizon of 3 years with a 5% discount rate, based on public health care institutions perspective. Results: The results of the model using a cohort of 200 hypothetic NHL patients, 100: aggressive-NHL and 100: indolent-NHL, in which 50% received treatment with R-CHOP and the other half with CHOP showed that the use of Rituximab in addition to the CHOP therapy in the case of patients with Aggressive NHL represents savings per patient in compete remission of USD$138,530.33. In the case of patients with Indolent NHL the savings were USD$1,366,417.78. Both savings represents the possibility to obtain 10 more patients in complete remission (3 and 7 respectively). Conclusion: The use of Rituximab in addition to CHOP as first line therapy for NHL is not only a cost-effective intervention when compared to CHOP therapy in the Mexican context, but, according to the results, it is also a cost-saving intervention with an average saving of USD$821,739.23.