Background The effect of pre-injury antiplatelet treatment in the risk of intracranial lesions in subjects after mild head injury (Glasgow Coma Scale (GCS) 14–15) is uncertain.

Methods The potential risk was determined, considering its increasing use in guidelines on cardiovascular disease prevention, and ageing of the trauma population in Europe.

Patients The interaction of antiplatelet therapy with the prediction variables of main decision aids was analysed in 14 288 consecutive adolescent and adult subjects with mild head injury.

Measurements Any intracranial lesion at CT scan was selected as an outcome measure in a multivariable logistic regression analysis.

Results Intracranial lesions were demonstrated in 880 cases (6.2%), with an unfavourable outcome at 6 months in 86 (0.6%). Antiplatelet drugs were recorded in 10% of the entire cohort (24.7% in the group over 65 years). They increased the risk of intracranial lesions in the univariate analysis (OR 2.6; 95% CI 2.2 to 3.1), interacting with age in the multivariate analysis (antiplatelet OR 2.7 (1.9 to 3.7); age ≥75 years 1.4 (1.0 to 1.9)). The inclusion of these two variables with those included in previous decision aids for CT scanning (GCS, neurodeficit, post-traumatic seizures, suspected skull fracture, vomiting, loss of consciousness, coagulopathy) predicted intracranial lesions with a sensitivity of 99.7% (95% CI 98.9 to 99.8) and a specificity of 54.0% (95% CI 53.1 to 54.8), with a CT ordering rate of 49.3% (undetermined events 0.2:1000).

Interpretation Antiplatelet drugs need to be considered in future prediction models on mild head injury, considering their increasing use and progressive ageing of the trauma population.