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Spinal cord injury (SCI) is a major cause of severe disability. This study aims to assess the effectiveness of a quality improvement program on neurological recovery after SCI. Before-after study during two phases was done in one intensive care unit in a university hospital. The quality improvement project comprised protective mechanical ventilation, early tracheostomy in anatomical injury above the sixth cervical vertebra, early enteral nutrition, early mobilization, and active perineal care in adult SCI patients. The primary endpoint was the difference between the American Spinal Injury Association (ASIA) motor score between discharge and intensive care unit (ICU) admission (Delta ASIA). Fifty-seven and 60 patients were included in the control and in the intervention period respectively. The ASIA motor score upon ICU admission was 16 (7–37) before and 11 (2–30) after the implementation (p = 0.30). The implementation phase was associated with lower tidal volumes (p < 0.001), higher positive end-expiratory pressure (p < 0.001), earlier tracheostomy (p = 0.01), earlier enteral nutrition initiation (p < 0.05), earlier mobilization (p < 0.05), and more active perineal care (p < 0.05). The Delta ASIA was +16 [4–32] after versus +6 [0–14] before the intervention (p < 0.05). After adjustment for potential cofounders, the intervention phase was significantly associated with higher Delta ASIA (β coefficient, 11.4; CI95 [1.9–21]; p = 0.01) in multi-variable analysis. No secular time trend unrelated to the intervention was highlighted. One year after trauma, the Delta ASIA was higher in the intervention period than in the control period (+34 [15–60] vs. +11 [0–33]; p < 0.05). After adjustment on potential confounders, an early in-ICU rehabilitation program in SCI patients was associated with higher neurological score upon ICU discharge. [ABSTRACT FROM AUTHOR]