Objectives: Knowledge regarding delirium prevention in patients with acute brain injury remains limited. We tested the hypothesis that an intervention bundle which targeted sedation, sleep, pain, and mobilisation would reduce delirium in patients with acute brain injury. Design: A prospective before-after intervention study: a five-month phase of standard care was followed by a six-month intervention phase. Setting: The neuro-intensive care unit, University Hospital of Copenhagen, Denmark. Main outcome measures: The Intensive Care Delirium Screening Checklist was used to detect delirium. Primary outcome was delirium duration; secondary outcomes were delirium prevalence, ICU length of stay and one year mortality. Results: Forty-four patients were included during the standard care phase, and 50 during the intervention phase. Delirium was present in 90% of patients in the standard care group and 88% in the intervention group (p = 1.0), and time with delirium was 4 days vs 3.5 days (p = 0.26), respectively. Also, ICU length of stay (13 vs. 10.5 days (p = 0.4)) and the one year mortality (21% vs 12% (p = 0.38))) were similar between groups. Conclusion: We found a high prevalence of delirium in patients with acute brain injury. The intervention bundle did not significantly reduce prevalence or duration of delirium, ICU length of stay or one year mortality.