g Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level ؋ 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.) G alactomannan (GM) is a polysaccharide component of the cell wall of filamentous fungi, including Aspergillus species. GM is hematogenously released by fungal hyphae during invasive growth. Serum GM detection has proved to be useful for the diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies (1-3).In contrast, data on the performance of GM testing with urine samples are limited. After promising results in an animal model nearly 3 decades ago (4), only very recent pilot studies have indicated that GM detection in urine may be promising for IA screening in humans (5-8). Besides important advantages, one of the potential major limitations of urine specimen testing is that GM dilutions in urine vary, thus influencing GM concentrations. Interestingly, previous studies on the diagnostic performance of urine GM determinations for IA did not take into account urine dilution, which may explain the inconsistent results (5-8). Urine creatinine concentrations vary depending on water intake and are used to determine reliably the concentrations of various analytes in urine when 24-hour urine collection is not feasible. Similar to serum creatinine findings, elevated urine creatinine concentrations can be found in conditions such as kidney failure, rhabdomyolyses, and pyelonephritis, as well as with a high-meat diet. The objective of this study was to evaluate urine GM testing and to determine whether the diagnostic performance of urine GM testing can be improved by the use of a creatinine-based urine GM ratio.(Data in the manuscript were presented, in part, at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2015, and the 7th Trends in Medical Mycology, Lisbon, Portugal, 2015.) This prospective single-center study was conducted at the Medical University Hospital of Graz (Graz, Austria) between September 2014 and August 2015. Adult patients (Ͼ18 years of age) who were admitted to the hematology or bone marrow transplantation ward and were at risk for IA (e.g., patients with prolonged neutropenia secondary to high-dose induction/myeloablative chemotherapy or patients with graft-versus-host disease) (9, 10) were identified and, after informed consent was obtained, were monitored prospectively using clinical rounds, chart reviews, and surveys of electronic documents, including microbiological test results. Patients' medical records were reviewed in...