OBJECTIVES: Use of proton instead of photon radiation therapy for head and neck cancer reduces the primary tumor and damage to adjacent organs risk, which results in fewer complications. These complications decrease quality of life (QOL). To support better decision making concerning which patients benefit most from proton therapy, a patient-level simulation model is developed and applied to compare outcomes. METHODS: Model estimates, such as patient and tumor characteristics, follow-up time, and survival, were based on patient-level data containing patients treated with radiation therapy as first line therapy for head and neck tumor in the Netherlands  between 1980–2010 at the UMC Groningen (n=277) and VU Amsterdam (n=736). In silico radiation treatment planning schemes for both proton and photon therapy allowed to compare a priori expected health benefits and cost consequences for both therapy modes to support a patient tailored choice. RESULTS: Patients experienced their first event at a median time of 30 (0-270, SD 34) months’ time. Loco-regional recurrency in 29%, distant metastasis in 4.2%, both combined in 1% and dead in 13.3% of patients. Cost per year for photon was estimated €15000, proton €30000, disease free state €190, local regional recurrence €28000, metastases €35000, and both €35000. For the complication sticky saliva costs per year of an average patient were €31, xerostomia €194, dysphagia €57, tube feeding €4262, and hypothyroidism € 117. Proton radiation therapy leads to less complications and improved QOL. CONCLUSIONS: Given the high costs of proton therapy, this was found not to be cost-effective compared to best photon therapy in an average patient with head and neck cancer. However, the outcomes vary substantially between patients. Depending on patient and tumor characteristics for selected patients with high complication risks, proton therapy can be a better option.