Background: B-large cell lymphoma (B-LCL) is the most common form of NHL. 5-year survival rates vary between 40 and >90% depending on prognostic factors but the importance of many of them is disputed. Those found most important and reproducible in the pre-rituximab era were included in the IPI. Since the original description, various variants of this index have been published. Aims: To reassess the value of the IPI, revised IPI (R-IPI), age-adjusted IPI (aaIPI), stage-adjusted IPI and different possible clinical prognostic factors in an unselected population of patients with B-LCL receiving rituximab containing front-line therapy. Methods: 371 patients diagnosed with B-LCL during 2007 and 2008 and treated with rituximab plus chemotherapy in 16 Croatian hematology departments were included in this study. Patients were registered at the time of treatment start, and data on demographics, clinical features and laboratory parameters collected. Follow-up was performed yearly. The study was approved by the Croatian Central Ethics’ Committee. Prognostic values of IPI, R-IPI, aaIPI, stage-adjusted IPI, individual factors used in indices (age, PS, LDH, stage, number of extranodal organs involved), bulk, gender, anemia, bone marrow infiltration and the presence of B symptoms were evaluated with respect to overall survival (OS) and progression-free survival (PFS) were evaluated. Survival analyses were performed using the Kaplan-Meier method and comparisons using the log-rank test. Multivariate analysis is ongoing. Results: 5-year OS and PFS of the whole cohort were 50% and 49.5%. Significant negative prognostic factors in univariate analyses for OS and PFS were: age>65, LDH high, PS>1, stage>2, Hb<120 g/l, male gender, bone marrow infiltration and presence of B symptoms. Number of involved extranodal sites and presence of bulky disease did not influence prognosis. Regarding prognostic indices, conventional IPI was most useful, distinguishing 4 categories with reasonable proportions of patients. R-IPI was less useful; the differences in PFS between the three prognostic categories were significant, but there was no difference in OS between patients with scores 0 and 1-2. aaIPI distinguished only two categories; patients with score 0 had excellent prognosis, while there was no difference in outcomes between those with scores 1 and 2-3. Stage adjusted IPI distinguished three prognostic groups, but very few patients had a score 0. Summary and Conclusions: Our study suggests that conventional IPI remains the most useful prognostic index. Bulky disease does not seem to be of prognostic importance, probably because of widespread use of adjuvant radiotherapy to initial bulky sites after immunochemotherapy. As seen in some other studies, men have a worse prognosis, possibly related to differences in rituximab metabolism. Additional negative prognostic factors include anemia, B symptoms and bone marrow infiltration, possibly as markers of aggressive systemic disease.