Introduction: The cardiovascular risk marker tissue plasminogen activator antigen (t-PA:Ag) can be reduced by long-term exercise interventions, but it is unknown, whether this is due to the weight loss induced by physical activity or due to the physical activity per se. Materials and methods: This was tested in 60 healthy, younger (20-40 years), overweight (BMI: 25-30 kg/m(2)) men randomly assigned to 12 weeks of intervention in one of four groups: training (T); energy-reduced diet (D); training and increased diet (T-iD); sedentary lifestyle and unchanged diet (controls, C). Fasting blood samples were obtained before and after 12 weeks of intervention and analyzed for plasma t-PA:Ag. Results: Body weight was reduced in groups T and D. We observed a decrease in t-PA:Ag from baseline to 12 weeks in all three exercise and diet intervention groups, and no change in the control group. A between-group difference in t-PA: Ag was observed at 12 weeks (p = 0.001), and this was due to lower values in T (p= 0.0005), D (p= 0.005) and T-iD (p= 0.009) compared with the control group. Total body fat mass was reduced in all three exercise groups, and we observed a positive correlation between changes in t-PA:Ag and changes in intra-abdominal and subcutaneous adipose tissue volume. Conclusions: Our results demonstrate that t-PA:Ag was reduced in all three intervention groups. This suggests that 12 weeks of endurance training per se, irrespective of concomitant weight loss, beneficially affects cardiovascular risk in healthy, younger, overweight men. (C) 2017 Elsevier Ltd. All rights reserved.