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To investigate the question of whether salvage therapy with the programmed cell death protein 1 (PD-1)–blocking antibodies nivolumab or pembrolizumab with or without bevacizumab offers clinical or survival benefit in patients with recurrent high-grade gliomas (HGGs).This was a single-institution retrospective observational study in 31 adult patients who received pembrolizumab (Keytruda) or nivolumab (Opdivo) with or without concurrent bevacizumab for recurrent high-grade glioma.Median progression-free survival (mPFS) from first anti–PD-1 dose was 3.2 months (95% confidence interval [CI] 2.2–4.2), and there was no difference in patients receiving nivolumab (mPFS 3.8 months, 95% CI 1.7–5.8) compared to patients receiving pembrolizumab (mPFS 2.3 months, 95% CI 1.7–2.8, log rank 3.1, p = 0.08). There was also no difference in mPFS if patients had previously received bevacizumab (mPFS 3.2 months, 95% CI 2–4.3) or were bevacizumab naive (mPFS 3.7, 95% CI 0–7.9, log rank 1.3, p = 0.3). The median survival from date of first anti–PD-1 dose was 6.6 months (95% CI 4.2–9.1).Salvage therapy with nivolumab or pembrolizumab with or without bevacizumab does not confer a survival benefit in this heavily pretreated unselected patient population. Until the results of the currently ongoing clinical trials become available, the use of PD-1–blocking antibodies should be considered in selected individuals only.This retrospective observational study provides Class IV evidence that for patients with recurrent HGGs, salvage therapy with nivolumab or pembrolizumab does not significantly improve survival.