PURPOSE: Results of a prospective, randomized controlled trial at our institute demonstrate an association between the dose to the left hippocampus and neurocognitive decline post-radiotherapy for patients with glioblastoma. To minimize the dose to the left hippocampus, a left hippocampus sparing model was created using RapidPlan (RP) and multi-criteria optimization (MCO). MATERIALS AND METHODS: For 147 patients with newly diagnosed glioblastoma treated with volumetric modulated arc therapy (VMAT), the left and right hippocampus were delineated. Ninety-seven of 147 VMAT plans were used to configure a RP model named HCS1. The remaining 50 VMAT plans were used for the model validation. All 97 plans were replanned with the HCS1 and further optimized using MCO (HCS1+MCO). MCO was used to explore the trade-off between reducing the left hippocampus mean dose and planning objectives for the targets and other organs-at-risk (OAR) for HCS1 plans. These plans were used to create a new model called HCS2. MCO and RP model configuration were done within the Eclipse treatment planning system. RESULTS: The final HCS2 model decreased the mean dose to the left hippocampus by 26% compared to clinically treated plans without reducing target coverage for 50 validation data. The mean dose to the left hippocampus decreased from 32.65 Gy in clinically treated plans, 30.45 Gy in HCS1-generated plans, and 24.04 Gy in HCS2-generated plans. The mean volume receiving 95% of the prescription dose (V95%) of the planning target volume was 99.08% ± 1.39% in clinically treated plans, 99.03% ± 1.37% in HCS1-generated plans, and 98.80% ± 1.48% in HCS2-generated plans. Mean dose to 0.1 cc of the brainstem improved from 45.91 Gy in clinically treated plans to 39.29 Gy in HCS2-generated plans. CONCLUSIONS: The RP model and MCO helps to decrease left hippocampus mean dose while maintaining the target volume coverage and OAR sparing comparable to clinically treated plans for glioblastoma patients.