Background: Prognosis of diffuse large B cell lymphoma (DLBCL) patients depends on lymphoma and patient-related risk factors, best summarized in IPI (International Prognostic Index). The aim of the study was to determine whether the average relative dose intensity (ARDI) of anthracycline containing regimen could be an IPI-independent prognostic factor. Methods: We analysed 223 white Caucasian DLBCL patients, who completed at least four cycles of first-line R-CHOP immunochemotherapy (Rituximab, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone). ARDI was calculated by specially developed software, in each individual patient, simultaneously with chemotherapy prescription. It allowed to address instantly all revealed causes of decreased ARDI. Importance of ARDI for progression-free/overall survival (PFS/OS) was evaluated. Results: ARDI was decreased due to prolonged interval between immunochemotherapy cycles caused by neutropenia and infections (absolute neutrophil count < 1,0 x 10⁹/l) in 49.32% (110/223) or reduction of cytostatic doses in 19.73% (44/223) patients mainly as the consequence of cardiotoxicity or neutropenia (85,18% and 14,81% respectively, estimating in the group of patients with reduced doses of cytostatics). Progression free and overall survival (PFS and OS) varied significantly for ARDI > 90%, 89-80% and < 80% respectively (p < 0.00001). Multivariate analysis confirmed that ARDI > 90% was an IPI independent predictor of prolonged PFS (Hazard Ratio (HR), Confidence Interval (CI): HR = 0.31; 95%CI: 0.20-0.47; p < 0.000001) and OS (HR = 0.32; 95%CI: 0.21-0.48; p < 0.000001). Even with real time ARDI analysis it was possible to maintain it above 90% in 161 of 223 patients (72%). Further improvement may be possible only after implementing primary neutropenia prophylaxis and primary cardioprotection. Conclusions: DLBCL patients with ARDI > 90% have significantly better outcome regardless of IPI, therefore we postulate to regard adequate dose density as an official recommendation.