PURPOSE: Thirty to forty percent of patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra-abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI) > or =0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC in this setting, but azole-resistant Candida species are emerging. The aim of this study was to explore the efficacy and safety of caspofungin for prevention of intra-abdominal IC in high-risk surgical patients. METHODS: Prospective non-comparative single-center study in consecutive adult surgical patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given until resolution of the surgical condition. Candida colonization index and CCI, occurrence of intra-abdominal IC and adverse events were monitored. RESULTS: Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The median duration of preventive caspofungin therapy was 16 days (range 4-46). The colonization index decreased significantly during study therapy, and the CCI remained <0.4 in all patients. Caspofungin was successful for prevention of intra-abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion). No drug-related adverse event requiring caspofungin discontinuation occurred. CONCLUSION: Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials.