Introduction: Invasive aspergillosis (IA) affects mainly patients with hematological malignancies and early diagnosis is crucial for timely treatment. Most diagnoses are based on clinical and mycological criteria, mostly galactomannan (GM) test in serum or bronchoalveolar fluid, which is performed in case of clinical suspicion or as routine screening in patients at high-risk who are not receiving anti-mold prophylaxis, for early detection of IA. The aim of this study was to assess in a real-world setting, the efficacy of bi-weekly serum GM screening for the early detection of IA. Methods: A retrospective cohort that included 80 adult patients treated at the Hematology department, Hadassah Medical Center, 2016-2020, with a diagnosis of IA. Clinical and laboratory data were collected from patients' medical files and the rate of GM-driven, GM- associated and non-GM-associated IA was calculated. Results: There were 58 patients with IA. The rate of GM-driven diagnosis was 6.9%, GM-associated 43.1%, and non-GM-associated 56.9%. The GM test as a screening tool had led to IA diagnosis in only 0.2% of screened serums with a number needed to screen in order to find one patient with IA of 490. Conclusion: Clinical suspicion outweighs GM screening as a tool for early diagnosis of IA. Nevertheless, GM has an important role as a diagnostic tool for IA.