Introduction Diabetes Mellitus is one of the major chronic diseases in Western societies, causing considerable comorbidity of cardiovascular diseases and premature death. Because of the variety of risk factors for diabetes mellitus and different macrovascular complications, the set of potentially interesting interventions is quite large. For policy makers with limited budgets, the question thus arises in what area of diabetes prevention, health care money is spent most effectively. Objective The aim of the present study was to review the literature on economic evaluation of interventions for prevention of diabetes type 2 or its macrovascular complications, to describe their results and to identify the interventions that require additional research. Methods A systematic review of the literature was conducted. The interventions were classified by type of prevention. The characteristics of the selected studies (with life years gained or quality adjusted life years as an outcome measure) were described in a database, to generate summary tables. To be included, studies had to give a full economic evaluation of effects of the intervention. All studies were scored for quality using the BMJ checklist. Results In total 23 studies with life years gained or quality adjusted life years as an outcome measure were selected. Two studies focused on primary prevention, one on screening, and 20 studies evaluated interventions for the prevention of macrovascular complications. Conclusions Tight blood pressure control is a cost effective intervention compared to less tight control. Medication to reduce both overweight and hyperglycemia was found to be cost saving to moderately cost-effective. Primary prevention of type 2 diabetes also appeared to be cost-effective and cost saving, but further research is needed because only two studies were available. The results of medication interventions to reduce overweight, to reduce hyperglycemia, and to reduce dyslipidemia vary considerably, warranting further economic analysis to identify cost-effective strategies.