Introduction: Rituximab-based immunochemotherapy has been the standard of care for Diffuse Large B– Cell Lymphoma (DLBCL) for over 25 years. Except for patients with more aggressive subtypes of this disease, the absolute majority of patients are treated with 6 cycles of R-CHOP chemotherapy. Eleven years ago, we published the results of the first 140 patients treated with this combination in our Institution between 2003-2010. Methods: In this paper, we will present the treatment results of 148 patients treated in the period between 2017-2021 and compare them with the historical control from the period 2003-2010. Results: In our series of 148 patients, 50.6% were male, median age 60 years (20-89). 36.2% of patients had an IPI score of low risk, medium-low 25%, medium-high 30% and high risk 8.7%. Non-GCB subtype was present in 57.4% of patients, 21.6% had GCB and 20.9% were unclassified. Complete response (CR) was achieved in 74.8% of patients, partial (PR) in 13.3% while 11.9% had disease progression (PD). The 3-year progression-free survival (PFS) was 69.1%, while the 3-year overall survival (OS) was 73.9%. If we compare the results from the period 2003-2010, the three-year PFS and OS were then 56.5% and 64%, respectively, which is numerically lower than in the new cohort 2017-2021 where the PFS was 69.1% and OS 73.9%. These results were achieved despite a greater number of low-risk patients (IPI score 0 and 1) 44.7% versus 36.2% in the 2003-2010 and 2017-2021 cohorts, respectively. Conclusions: Although systemic therapy for DLBCL is basically similar, better treatment outcomes were achieved in the cohort treated an average of 13 years later. The reason probably lies in the greater utilization of PETCT imaging, more precise utilization of radiotherapy, better pathohistological andmolecular diagnostics, and potentially more adequate symptomatic therapy.