To assess the incidence and outcome of clinically significant aspiration pneumonitis in intensive care unit (ICU) overdose patients and to identify its predisposing factors. Retrospective cohort study. Medical ICU of an academic tertiary care hospital. A total of 273 consecutive overdose admissions. Clinically significant aspiration pneumonitis was defined as the occurrence of respiratory dysfunction in a patient with a localised infiltrate on chest X-ray within 72 h of admission. In our cohort we identified 47 patients (17%) with aspiration pneumonitis. Importantly, aspiration pneumonitis was associated with a higher incidence of cardiac arrest (6.4 vs 0.9%; p = 0.037) and an increased duration of both ICU stay and overall hospital stay [respectively: median 1 (interquartile range 1–3) vs 1 (1–2), p = 0.025; and median 2 (1–7) vs 1 (1–3), p < 0.001]. In multivariate logistic regression analysis, Glasgow Coma Scale (GCS) score [odds ratio (OR) for each point of GCS 0.8; 95% confidence interval (CI) 0.7–0.9; p = 0.001], ingestion of opiates (OR 4.5; 95% CI 1.7–11.6; p = 0.002), and white blood cell count (WBC) (OR for each increase in WBC of 109/l 1.05; 95% CI 1.0–1.19; p = 0.049) were identified as independent risk factors. Clinically relevant aspiration pneumonitis is a frequent complication in overdose patients admitted to the ICU. Moreover, aspiration pneumonitis is associated with a higher incidence of cardiac arrest and increased ICU and total in-hospital stay.