OBJECTIVE To explore the potential long-term health and economic consequences of lifestyle interventions for diabetic patients. RESEARCH DESIGN AND METHODS A literature search was performed to identify interventions for diabetic patients in which lifestyle issues were addressed. We selected recent (2003–2008), randomized controlled trials with a minimum follow-up of 12 months. The long-term outcomes for these interventions, if implemented in the Dutch diabetic population, were simulated with a computer-based model. Costs and effects were discounted at, respectively, 4 and 1.5% annually. A lifelong time horizon was applied. Probabilistic sensitivity analyses were performed, taking account of variability in intervention costs and (long-term) treatment effects. RESULTS Seven trials with 147–5,145 participants met our predefined criteria. All interventions improved cardiovascular risk factors at =1 year follow-up and were projected to reduce cardiovascular morbidity over lifetime. The interventions resulted in an average gain of 0.01–0.14 quality-adjusted life-years (QALYs) per participant. Health benefits were generally achieved at reasonable costs (=€50,000/QALY). A self-management education program (X-PERT) and physical activity counseling achieved the best results with =0.10 QALYs gained and =99% probability to be very cost-effective (=€20,000/QALY). CONCLUSIONS Implementation of lifestyle interventions would probably yield important health benefits at reasonable costs. However, essential evidence for long-term maintenance of health benefits was limited. Future research should be focused on long-term effectiveness and multiple treatment strategies should be compared to determine incremental costs and benefits of one over the other.