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This study aimed to clarify the clinicopathological prognostic parameters of de novo diffuse large B-cell lymphoma (DLBCL) in the rituximab era. We examined the correlation of 22 clinicopathological parameters with progression-free survival (PFS), overall survival (OS), and primary refractory disease in 285 DLBCL patients treated with rituximab-containing chemotherapy. Complete response rate was 87%, overall response rate was 91%, 5-year PFS rate was 72%, and 5-year OS rate was 91%. By log–rank test, higher International Prognostic Index (IPI) (P < 0.0001), Bcl-2 positivity (P = 0.0013), Bcl-6 negativity (P = 0.0112), and no irradiation (P = 0.0371) were significantly correlated with shorter PFS; higher IPI (P = 0.0107), starry sky pattern (P = 0.0466), and no irradiation (P = 0.0264) correlated with shorter OS. In multivariate analyses, higher IPI (P = 0.0006), Bcl-2 positivity (P = 0.0015), and Bcl-6 negativity (P = 0.04) were significantly correlated with shorter PFS; higher IPI (P = 0.0045) correlated with shorter OS. Bcl-2 (P = 0.0029), Bcl-6 (P = 0.002), and IPI (P < 0.0001) were significantly correlated with primary refractory disease. In conclusion, Bcl-2 positivity, Bcl-6 negativity, and higher IPI were indicators of shorter PFS and OS plus primary refractory disease in patients with DLBCL in the rituximab era.