This large, randomized, multicenter trial compared voriconazole, a second-generation triazole, with liposomal amphotericin B as empirical antifungal therapy for 837 patients with persistent fever and neutropenia. The success rates in terms of composite outcome were similar: 26.0 percent with voriconazole and 30.6 percent with amphotericin B. There were fewer breakthrough fungal infections among those treated with voriconazole (1.9 percent vs. 5.0 percent). In this large, randomized trial, the success rates were similar with voriconazole and with amphotericin B. Invasive fungal infections are important causes of morbidity and mortality among patients receiving cancer chemotherapy or undergoing bone marrow or stem-cell transplantation. 1 – 3 Over the past two decades, empirical antifungal therapy with conventional amphotericin B or liposomal amphotericin B has become the standard of care in reducing invasive fungal infections in patients with neutropenia and persistent fever. 4 – 9 Amphotericin B, however, is associated with significant dose-limiting nephrotoxicity and infusion-related reactions. Liposomal amphotericin B is equivalent to conventional amphotericin B for use as empirical antifungal therapy and significantly reduces proven invasive fungal infections, nephrotoxicity, and infusion-related reactions. 10 , 11 The high acquisition . . .