Summary Aspirin has been found to improve outcomes in an animal model of transfusion-related acute lung injury. We examined the association of aspirin use before admission to the intensive care unit and the development of transfusion-related acute lung injury in critically ill patients. We performed a post-hoc analysis of a nested case-control study that had been undertaken in a tertiary referral hospital. Transfusion-related acute lung injury cases were matched with controls (transfused patients not developing lung injury). Of these 218 patients, 66 used aspirin (30%). Use of aspirin did not alter the risk of transfusion-related acute lung injury after transfusion of platelets (OR 1.06, CI 0.59-1.91, p = 0.85), plasma (OR 1.06, 95% CI 0.59-1.92, p = 0.84), or red blood cells (OR 1.09, 95% CI 0.61-1.94, p = 0.77). Adjustment for confounding variables using propensity scoring also did not affect the risk of acquiring transfusion-related acute lung injury (p = 0.66). In conclusion, aspirin did not protect against transfusion-related lung injury in this cohort of critically ill patients.