Abstract Background There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. Methods NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. Results A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65–88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7–13.4) in the experimental arm and 11.8 months (95% CI, 8.3–14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54–1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Conclusions Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.