OBJECTIVES: Aim of this study was to evaluate cost-effectiveness of rituximab + CHOP (R-CHOP) versus CHOP, in patients affected by aggressive Non-Hodgkin lymphoma, in the Italian NHS’ perspective. METHODS: The economic analysis is based on an existing Markov model which was developed in order to evaluate costs and effects for two hypotetical cohorts of patients of age respectively higher and lower than 60 years, over a time frame of 15 years after administration of chemotherapy. The model is based on 5 health states (start therapy, complete response, no response, progression, death) and combines efficacy data from published clinical trials (GELA-98-5) with utilities from the literature and cost of therapies and medical follow-up after chemotherapy, based on Italian treatment patterns. Costs and effects were discounted respectively at 6% and 1,5%. Extensive 1-way and Monte Carlo sensitivity analyses were conducted in order to test the robustness of results. RESULTS: For the 2 cohorts (60+; 60-), incremental discounted Life Years Gained with R-CHOP versus CHOP were respectively 1.08 and 1.02 years; incremental QALYs were 1.15 and 1.04; the incremental cost/patient was 14.838€ and 13.938€; the incremental cost/LYG was therefore 13.732€ and 13.717€ and the incremental cost/QALY was 12.879€ and 13.362€, respectively for 60+ and 60- patients. CONCLUSIONS: The clinical advantage of R-CHOP is supported by incremental cost/LYG and cost/QALY ratios which fall well below all the thresholds commonly indicated for these values both in the international and italian literature. R-CHOP is a substantial improvement in the treatment of aggressive NHL, at a reasonable cost, in the perspective of the Italian NHS.