OBJECTIVES: PET-based radiotherapy planning for selective lymph node irradiation is an example of the current tendency to individualize treatment in cancer. We evaluated the cost-effectiveness of individualized radiotherapy planning, comparing PET-CT-based to CT-based radiotherapy treatment planning in non-small cell lung cancer. METHODS: Our analysis uses a previously developed decision model. The model was based on data for 200 NSCLC patients with inoperable stage I-IIIB, provided by the Maastro Clinic. Transition rates in the model were estimated by multi-state statistical modelling and include the impact of patient and tumour features on disease progression. Resource use estimates, costs and utilities were obtained from the database of the Maastro Clinic, the literature and Dutch guidelines. Primary outcomes were the difference in life years (LY), quality adjusted life years (QALY), costs and the incremental cost-effectiveness and cost-utility ratio (ICER and ICUR) of PET-CT versus CT based radiotherapy planning. Model outcomes were obtained from averaging the outcome for 50 000 simulated patients. To present uncertainty, a probabilistic sensitivity analysis was done. In scenario analyses, we explored the effect of varying the input parameters for costs and QALYs and the effect of changing the assumptions regarding the multi-state model. RESULTS: The incremental costs of PET-CT based planning were € 534 (95% CI: €-4670 – €6080) for 0,43 incremental LYs (95% CI: 0,31 – 0,52) and 0,33 QALYs gained (95% CI: 0,26 – 0,45). The base-case scenario resulted in an ICER of € 1242 per LY gained and an ICUR of € 1618 per QALY gained. The probabilistic sensitivity analysis gave a 41% probability that PET-CT based planning improves health outcomes at reduced costs and a 59% probability that PET-CT based planning is more effective at slightly higher costs. CONCLUSIONS: PET-based radiotherapy planning for non-small cell lung cancer is highly cost-effective compared to CT-based planning.