The clinical use and tolerability of voriconazole in daily practice for the treatment of fungal infection in critically ill patients was assessed in an open-label, non-comparative, observational study. All patients admitted to medical-surgical Intensive Care Units (ICUs) of 21 hospitals in Spain between February 2003 and January 2004, who were treated with voriconazole because of known or suspected fungal infection, were included. A total of 130 patients received voriconazole (6.2 cases per ICU). Fungal infections were classified as proven in 50 patients (38.5%) and probable in 38 (29.2%). The etiology was established in 103 patients, with Candida albicans and Aspergillus fumigatus as the most common pathogens. In 98 (75.4%) patients, voriconazole was initially administered intravenously. Fifty-three patients (40.8%) were treated with other antifungal agents prior to the use of voriconazole. In 21 patients (16.2%), voriconazole was administered in combination with other antifungal drugs. Clinical responses were cure and improvement in 65 (50%) patients, failure in 26 (20%), and undetermined in 39 (30%). The crude ICU mortality was 49.2%. According to multivariate analysis, ICU mortality was significantly associated with pneumonia (OR = 3.30, 95% CI 1.07-10.18) and infection caused by Aspergillus spp. (OR = 3.70, 95% Cl 1.12-12.28), whereas eradication of the causative microorganisms was inversely associated (OR = 0.13, 95% CI 0.05-0.34). Adverse events were recorded in 65 patients, probably or possibly related to the study drug in 21. In conclusion, in critically ill patients admitted to the ICU, the use of voriconazole was affective in 50% of cases. The drug was well tolerated and discontinuation of voriconazole treatment due to adverse events was not necessary.