BACKGROUND AND METHOD Hypotension and hyperglycaemia occurring in the first 24h after severe head injury are individually associated with poor outcome but a causal effect has not been proven for either. Their combined effect is unknown and is investigated in this observational study of 338 patients with head injury, a Glasgow coma score (GCS) of 8 or less and requiring mechanical ventilation. RESULTS Mean arterial pressure (MAP) and blood glucose are linearly related to mortality (P<0.0001). Regression analysis shows that each has an independent effect. Moreover, the relationship between blood glucose and mortality is stronger than the relationship between MAP and mortality. When patients are grouped according to lowest MAP, hyperglycaemia is associated with increasing mortality within each group (P<0.0001). CONCLUSION Further studies on the combined effect of hyperglycaemia and hypotension on mortality after head injury are needed because this study suggests, but does not prove, an additive, causal association.