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We conducted a randomized surgical window-of-opportunity trial ( NCT04606316 ) in recurrent, resectable glioblastoma. Between 2021 and 2024, 71 patients were screened, and 63 were randomized (intention-to-treat [ITT] population), and 58 received study treatment. Patients received pre-surgical immune checkpoint blockade (ICB) with dual anti-PD1 nivolumab + anti-CTLA4 ipilimumab (Arm 1), nivolumab alone (Arm 2), or placebo (Arm 3). Following surgery, Arms 1 and 3 received dual ICB, while Arm 2 continued nivolumab until progression or unacceptable toxicity. The primary endpoint, tumor-infiltrating lymphocyte (TIL) density, was met for Arm 1, as neoadjuvant dual ICB significantly increased TIL density compared with untreated control (Arm 3). As a secondary endpoint, median overall survival in the ITT population was 402 days (95% CI, 265-571) among patients who received dual ICB (Arms 1 and 3) and 273 days (95% CI, 166-506) for those assigned to nivolumab alone (Arm 2). No unanticipated toxicities were observed. Exploratory analyses showed that dual ICB elicited robust intratumoral and systemic immune activation, including increased interferon-related gene expression in blood. Higher TIL density and early systemic interferon-signature induction were associated with improved survival, whereas tumor mutational burden was not. Our results demonstrate pharmacodynamic activity of dual ICB in glioblastoma, with survival outcomes comparing favorably to similar studies.