Candida albicans biofilms complicate the treatment of infected implanted intravascular devices because of decreased antifungal susceptibility. In our investigation, 48 rabbits with experimental central venous catheter C. albicans infection were equally allocated to a control arm or to receive amphotericin B deoxycholate or caspofungin treatment while undergoing systemic and intraluminal lock therapy for 7 days. C. albicans was cultured from catheters from all control rabbits, from 3 that received amphotericin B, and from 0 that received caspofungin. Differences in colony counts were detected between the control and amphotericin (P<.001) and control and caspofungin (P<.001) arms. Caspofungin may be useful in the treatment of C. albicans biofilm-associated intravascular catheter infections, which warrants further study.