Autopsy studies show that IA is among the most commonly missed diagnoses in critically ill patients. And, because of lack of unequivocal diagnostic criteria, a timely diagnosis remains challenging. We investigate the epidemiology of and the clinical risk factors for IA in critically ill patients. We conducted a retrospective, observational study of all consecutive ICU patients with evidence of IA in the postmortem examination. During the period of the study (25 years), 893 postmortem examinations were performed in the ICU. Twenty-five patients (2.8%) were diagnosed with IA in autopsy. Only ten (40%) were classified as IA ante-mortem, based on the initiation of antifungal treatment. The most common comorbid conditions were corticosteroid treatment (n = 14, 56%), chronic obstructive pulmonary disease (COPD) (n = 11, 44%), immunosuppression (n = 6, 24%) and haematological malignancy (n = 5, 20%). Twenty-three patients (92%) had three or more risk factors for IA. Critically ill patients with pulmonary infiltrates, treated with high doses intravenous corticosteroids (even for a short period of time), particularly COPD patients who developed worsening respiratory insufficiency despite appropriate treatment were at the highest risk of IA.