Résumé : In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016–March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPi—alone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictors—to prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1–3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90–100)) at day 3 (sensitivity 24% (15–35), negative predictive value 36% (34–39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information.