Invasive fungal infections are frequent complications in patients with hematologic malignancies due to immunosuppression and intensive treatments. In Colombia, limited diagnostic availability, heterogeneous prescribing practices, and emerging antifungal resistance highlight the need for optimized use. We evaluated an interdisciplinary antifungal stewardship intervention in the hematology unit of a tertiary-care hospital. A quasi-experimental before-and-after study included 353 hospitalized patients receiving systemic antifungals between 1 January 2023 and 31 December 2024 (1154 prescriptions). Following the intervention, antifungal prescribing shifted toward increased prophylaxis and reduced therapeutic use, with substantial reduction in prophylactic Amphotericin B dosing, stable treatment dosing, and selective changes in agent choice, including decreased voriconazole and discontinuation of some broad-spectrum drugs. Microbiological sampling decreased, reflecting a more targeted diagnostic approach rather than improved documentation. Antifungal consumption patterns showed redistribution among agents rather than uniform reduction. Prophylaxis-related costs increased, while treatment-related costs decreased without statistical significance. ICU admissions and in-hospital mortality remained unchanged. These results demonstrate that structured antifungal stewardship programs are feasible and safe in hematology units in middle-income settings, supporting more rational antifungal use without compromising patient outcomes.