Abstract Background There is a consensus that younger patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens including high-dose cytarabine, rituximab and high-dose chemotherapy with stem cell support, but the optimization of treatment for elderly or unfit patients, as well as patients with localized or indolent disease, remains a challenge. Methods Our study is based on data from the Swedish and Danish Lymphoma Registries from the period of 2000-2011, in Sweden supplemented by review of patients´ records. The Lymphoma Registries comprise >95% of all diagnosed lymphoma patients in Sweden and Denmark. Results 1389 patients were diagnosed with MCL, confirmed by positive cyclin-D1 and CD5 staining, in Sweden and Denmark between 2000 and 2011. In this population based cohort, we could confirm the prognostic impact of MIPI, but in addition, male sex was associated with inferior overall survival (OS) in multivariate analysis (HR 1.4, p<0.001). Treatment with the Nordic MCL2 regimen (n=324) was associated with superior outcome compared to the majority of other regimens (3-year OS: 80%). In patients >65 years, chlorambucil (n=132) was superior to CVP (n=35) (HR 1.8, p=0.003), when adjusted for MIPI and rituximab, but there was no significant difference between CHOP (n=311) and CHOP+Cytarabine (n=84). Rituximab (HR 1.5, p<0.001) and autologous stem cell transplantation (HR 1.9, p<0.001 ) per se were both associated with prolonged OS in multivariate analysis. Forty-three (3.1%) patients with stage I-II disease received radiotherapy as primary treatment with curative intent showing an estimated 3-year OS of 93%. A small proportion, 29 patients (2.1%), were followed without treatment. Estimated 3-year OS for this group of patients was 79%. Conclusion By a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice. Disclosures: No relevant conflicts of interest to declare.