ABSTRACT Beta-(1,3)- d -glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI ( P < 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population.