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Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces.