Background: Fruits and vegetables are an essential part of the human diet, but many people do not consume the recommended serves to prevent cardiovascular disease and cancer. In this research, we evaluate the cost-effectiveness of interventions to promote fruit and vegetable consumption to determine which interventions are good value for money, and by how much current strategies can reduce the population disease burden. Methods/Principal Findings: In a review of published literature, we identified 23 interventions for promoting fruit and vegetable intake in the healthy adult population that have sufficient evidence for cost-effectiveness analysis. For each intervention, we model the health impacts in disability-adjusted life years (DALYs), the costs of intervention and the potential cost-savings from averting disease treatment, to determine cost-effectiveness of each intervention over the lifetime of the population, from an Australian health sector perspective. Interventions that rely on dietary counselling, telephone contact, worksite promotion or other methods to encourage change in dietary behaviour are not highly effective or cost-effective. Only five out of 23 interventions are less than an A$50,000 per disability-adjusted life year costeffectiveness threshold, and even the most effective intervention can avert only 5% of the disease burden attributed to insufficient fruit and vegetable intake. Conclusions/Significance: We recommend more investment in evaluating interventions that address the whole population, such as changing policies influencing price or availability of fruits and vegetables, to see if these approaches can provide more effective and cost-effective incentives for improving fruit and vegetable intake. © 2010 Cobiac et al.