Background: Panic disorder affects many people, is associated with a formidable disease burden, and imposes costs on society. The annual influx of new cases of panic disorder is substantial. From the public health perspective it may therefore be a sound policy to reduce the influx of new cases, to maintain the quality of life in many people, and to avoid the economic costs associated with the full-blown disorder. For this purpose, prevention is needed. Here we present the first economic evaluation of such an intervention. Methods: Randomised trial of 117 people with panic disorder symptoms not meeting the diagnostic criteria of DSM-IV panic disorder. The interventions were time-limited cognitive-behavioural therapy v care-as-usual. The central clinical endpoint was DSM-IV panic disorder-free survival over 3 months. Costs were calculated from the societal perspective. Using the bootstrap method, incremental cost-effectiveness ratios were obtained, placed in 95% confidence intervals, projected on the cost-effectiveness plane, and presented as acceptability curves. Results: The median incremental cost-effectiveness ratio is €6,198 (95% CI 2,435 - 60,731) per PD-free survival gained, which has a likelihood of 75.2% of being more acceptable from a cost-effectiveness point of view than care-as-usual when a willingness-to-pay ceiling is assumed of €10,000 per PD-free survival. The most significant cost driver was therapists' time. A sensitivity analysis indicated that cost-effectiveness improves when the number of therapist hours is reduced. Conclusion: This is the first economic evaluation alongside a prevention trial in panic disorder. The small sample (n = 117) and the short time horizon of 3 months preclude firm conclusions, but our findings suggest that the intervention may be acceptable from a cost-effectiveness point of view, especially when therapist involvement can be kept minimal. Nevertheless, our results must await replication in a larger trial with longer follow-up times before we can confidently recommend implementation of the intervention on a broad scale. In the light of our findings and given the burden of panic disorder, such a new trial is well worth the effort. © 2009 Smit et al; licensee BioMed Central Ltd.