OBJECTIVES: Evidence suggests that response-guided neoadjuvant chemotherapy (RG-NACT) with magnetic resonance imaging (MRI) is effective in treating oestrogen receptor positive/human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer patients. We estimated the expected cost-effectiveness and resource requirements of implementing RG-NACT with MRI vs. conventional-NACT for treatment of ER+/HER2- breast cancers in the Netherlands (NL). METHODS: A Markov-model was developed to analyse the incremental costs/QALY from a hospital perspective over a 5-year time horizon. Health services required (MRI scans performed, MRI technologists, breast radiologists and confirmatory scans) for and health outcomes (prevented relapses, prevented deaths, patients with adverse events or contraindications and MRI technologists with adverse events) of implementing RG-NACT were estimated via resource modelling analysis considering the current (4%) and a full implementation (100%) scenario in the Dutch population of ER+/HER2- breast cancer women (n=6306). RESULTS: RG-NACT is expected to generate 0.001 and 0.07 QALYs and save €8 and €341 costs for the 4% and 100% implementation scenarios respectively. At current implementation rate, 213 MRI examinations, 273 MRI technologists and 1 breast radiologist are required to prevent 0.4 relapses and 6 cancer deaths. At full implementation, a 25-fold increase in MRI examinations is projected, requiring ~5 times higher MRI utilization and 6560 additional MRI technologists, which is expected to prevent 10 additional relapses (+2400%) and 169 cancer deaths (+2400%). Increasing implementation rates markedly increased the number of confirmatory scans (+901), contraindications (+932) and MRI technologists experiencing adverse events (+1706) by 25-fold, and decreased the number of patients with adverse events (-29) by 1.3-fold. CONCLUSIONS: RG-NACT likely dominates conventional-NACT at current and full implementation rates. Full implementation generates a 25-fold increase in additional health benefits, but requires MRI capacity in the Netherlands to be increased 5-fold, which is challenging given a shortage of MRI technologists.