BACKGROUND Patients <60 years old with high-risk diffuse large B-cell lymphoma (DLBCL) receiving standard RCHOP(E) treatment display high relapse rates. Here, we compared this standard regimen to a high-intensity regimen in terms of recurrence and long-term survival. MATERIAL AND METHODS Newly diagnosed DLBCL patients <60 years old who were treated at the Second Hospital Affiliated with Xi'an Jiaotong University between January 2004 and December 2013 (n=198, 18-60 years) were included in the study. The high-intensity group included 107 patients (54.0%) who received >8 courses of chemotherapy (high-dose CHOP, CHOP-E, EPOCH, MAED, MMED, and HyperCVAD). The control group included 91 patients (46.0%) who received 6-8 courses of CHOP-based treatment. Response rate (RR), survival, relapse, and adverse effects were compared. RESULTS Baseline characteristics of the patients were similar between the 2 groups. Median follow-up was 64.5 months. RR in the high-intensity and control groups was 88.8% and 84.6% (P=0.387), respectively; 5-year overall survival was 66.4% and 36.3% (P<0.001), respectively; 5-year progression-free survival was 56.1% and 28.6% (P<0.001), respectively; 5-year disease-free survival was 54.2% and 24.2% (P<0.001), respectively; and relapse rate during follow-up was 29.5% and 67.5% (P<0.001), respectively. There were no significant differences in adverse effects between the 2 groups. CONCLUSIONS High-intensity chemotherapy is associated with better prognosis of patients <60 years old with newly diagnosed high-risk DLBCL.