Background: Hyperglycaemia is common in acute severe traumatic brain injury (sTBI) and has been strongly correlated with neurotoxicity and unfavourable outcomes. Studies investigating intensive insulin therapy (IIT) in sTBI patients are sparse and consensus has not been achieved. We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) investigating the use of IIT in acute sTBI to determine the benefits and harms of maintaining strict normoglycaemia. Methods: We searched MEDLINE, EMBASE, CENTRAL and BIOSIS for RCTs comparing IIT with conventional insulin therapy (CIT). Primary outcomes were in-hospital and long-term (≥ 6 months) mortality and unfavourable neurological outcome (Glasgow outcome scale (GOS) 1-3 or extended GOS (eGOS) 1-4 at ≥ 6 months). Secondary outcomes included rate of hypoglycaemia, rate of ICU infection and ICU length of stay. Results were pooled and presented as relative risks (RR) with 95% confidence intervals (95% CI) using random-effects models. Results: We identified 2848 records, of which 3 (n = 416) studies met inclusion criteria. Maintenance of normoglycaemia in acute sTBI with IIT does not reduce mortality during hospitalization (3 studies, n = 416; RR 1.02, 95% CI 0.73 to 1.42; I2 0%) or at 6 months (3 studies, n = 408; RR 0.97, 95% CI 0.78 to 1.22; I2 0%) when compared to CIT. However, IIT is associated with a statistically nonsignificant reduction in unfavourable GOS (3 studies, n = 409; RR 0.91, 95% CI 0.80 to 1.03; I2 0%). Patients under IIT have significantly reduced ICU infection rates. The incidences of both standard (≤ 80 mg/dL) and severe hypoglycaemia (≤ 40 mg/dL) are higher in IIT arms, though neither analysis is statistically significant. Conclusions: There is no difference between in-hospital or long-term mortality of acute sTBI patients treated with IIT compared to those treated under CIT. IIT may possibly result in modestly reduced morbidity, but this analysis did not reach statistical significance. The rate and impact of hypoglycaemia in IIT is unclear and further RCTs are required to evaluate the benefits and harms of IIT before its clinical implementation in acute sTBI management.