OBJECTIVES: To perform a CE evaluation of the use of CHOP vs R-CHOP for the treatment of aggressive NHL stages III and IV. METHODS: After a review of the medical literature about the economic impact of NHL treatment, we performed an analysis of the resources consumed by 116 patients with the diagnostic of NHL during 2004 in the Mex-INCan. The economic evaluation was done using an hypothetical cohort simulation through a five years by means of Markov Model with monthly transitions, using a five percent discount rate. The model included 11 health status: Diagnostic; 1st-line treatment, 1st-remission, 1st-relapse, 1st-progression, 2nd-line treatment (salvage therapy), 2nd-remission, 2nd-relapse, 2nd-progression, 3rd-line treatment (salvage therapy) and dead. RESULTS: The direct medical cost included diagnostic and stratification USD$2,152.01 ($2,016.77-$2,287.26); 1st-line CHOP [7.19 cycles (6.97-7.42)] USD$841.17 ($813.03-$869.31); R-CHOP [7.20 cycles (6.32-8.08)] USD$17,823.19 ($12,670.83-$22,975.55); 1st-salvage treatment (Bone Marrow Transplant, BEAM scheme) USD$56,174.10; 2nd-salvage treatment ICE-Scheme USD$18,162.34, DHAP-Scheme USD$4,138.10; ESHAP-Scheme USD$3,730.22; and monthly cost of support therapy and follow-up USD$382.15 ($301.74-$462.57). The estimated management cost at the fifth year was USD$59,785.68 for R-CHOP and USD$52,966.70 for CHOP. The CE rate for the use of R-CHOP vs CHOP was USD$6,526.54 for each free-progression year, a clear trend toward the use of monoclonal antibody inclusion. CONCLUSIONS:Long term results are fundamental for any evaluation of NHL treatment scheme. Under this scenario, the increase in the free-progression survival and global survival, with R-CHOP a CE ratio under one GDP per-capita in Mexico (USD$7,785.89– A WHO accepted threshold) for every free-progression year gained and it is evident that this treatment is cost-effective.