Aims/hypothesis: Long-term follow-up of the Steno-2 study demonstrated that intensified multifactorial intervention increased median lifespan by 7.9 years and delayed incident cardiovascular disease by a median of 8.1 years compared with conventional multifactorial intervention during 21.2 years of follow-up. In this post hoc analysis of data from the Steno-2 study, we aimed to study the difference in direct medical costs associated with conventional vs intensified treatment. Methods: In 1993, 160 Danish individuals with type 2 diabetes and microalbuminuria were randomised to conventional or intensified multifactorial target-driven intervention for 7.8 years. Information on direct healthcare costs was retrieved from health registries, and the costs in the two groups of participants were compared by bootstrap t test analysis. Results: Over 21.2 years of follow-up, there was no difference in total direct medical costs between the intensified treatment group, €12,126,900, and the conventional treatment group, €11,181,700 (p = 0.48). The mean cost per person-year during 1996–2014 was significantly lower in the intensified treatment group (€8725 in the intensive group and €10,091 in the conventional group, p = 0.045). The main driver of this difference was reduced costs associated with inpatient admissions related to cardiovascular disease (p = 0.0024). Conclusions/interpretation: Over a follow-up period of 21.2 years, we found no difference in total costs and reduced cost per person-year associated with intensified multifactorial treatment for 7.8 years compared with conventional multifactorial treatment. Considering the substantial gain in life-years and health benefits achieved with intensified treatment, we conclude that intensified multifaceted intervention in high-risk individuals with type 2 diabetes seems to be highly feasible when balancing healthcare costs and treatment benefits in a Danish healthcare setting.