Young patients with diffuse large B-cell lymphoma (DLBCL) are variably treated with rituximab combined with cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP), CHOP-etoposide (R-CHOEP), and anthracycline-based regimens with the addition of high-dose cytarabine/methotrexate (R-HDA/M). Using the nationwide, population-based Swedish Lymphoma Registry, we evaluated outcome, by treatment and Healthcare Region, in all 751 DLBCL patients aged ≤60 years without central nervous involvement, diagnosed in Sweden between 2007 and 2012. Overall survival was estimated using multivariate Cox analysis. In patients with age-adjusted international prognostic index (aaIPI) ≥ 2, the 5-year overall survival (OS) was 70%, 76% and 85% after R-CHOP, R-CHOEP and R-HDA/M, respectively (P = 0·002); the corresponding estimates were 40%, 55%, and 92% in aaIPI = 3 (P = 0·014). There were large therapeutic differences between Sweden's six Healthcare Regions for aaIPI ≥ 2: three were “Moderate” (more R-CHOP) and three “Intensive” (more R-CHOEP and R-HDA/M). Patients with aaIPI ≥ 2 who were treated in the Intensive Regions, showed better OS (P < 0·00005), particularly those with aaIPI = 3 (5-year OS, 62% vs. 30%; P < 0·00005). There were no regional differences in therapy or survival in patients with aaIPI < 2. We conclude that in younger high-risk patients, survival appears superior after more intensive therapy than R-CHOP.