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Objectives: Primary graft dysfunction (PGD) affects survival after lung transplant (LT). The current hypothesis was that prone positioning (PP), proposed as a rescue maneuver to treat refractory hypoxemia due to PGD, may improve LT outcomes, especially when applied early., Design: Bilateral LT recipients developing moderate-to-severe PGD within 24 hours from intensive care unit admission were enrolled. From January 2020 to November 2021, patients developing PGD after LT were turned prone between 24 and 48 hours after diagnosis, only in case of radiological or oxygenation worsening ("late PP" group). After November 2021, patients were routinely turned prone within 24 hours from PGD diagnosis ("early PP"). A propensity score-weighted analysis, adjusted for clinically relevant covariates, was applied., Setting: Intensive care unit., Participants: Bilateral LT recipients., Interventions: Early PP, late PP, or supine position., Measurements and Main Results: 130 LT patients were screened and 67 were enrolled. A total of 25 (37%) recipients were treated in the supine position, 24 (36%) in early PP, and 18 (27%) in late PP. After propensity score weighting, both supine treatment (estimated effect for 1 ventilator-free day = 8.23, standard error: 2.97, p = 0.007) and early PP treatment (estimated effect = 9.42, standard error: 2.59, p < 0.001) were associated with greater 28-day ventilator-free days than late PP treatment (reference). Compared with late PP, early PP was also associated with better oxygenation, driving pressure, and static respiratory system compliance. Compared with supine recipients, the early PP group showed better oxygenation at 72 hours after PGD diagnosis., Conclusions: Early PP in LT recipients with moderate-to-severe PGD seems to be associated with better 28-day ventilator-free days, oxygenation, and driving pressure than late PP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)