ObjectivesThis study aims to assess the urinary diffusion and clinical effectiveness of voriconazole in patients with fluconazole-resistant urinary candidiasis. Patients and methodsIn this prospective pilot study, we utilized a validated chromatography method to measure voriconazole in urine over a 12-hour period between two administrations of the drug and in plasma at trough. ResultsThirty-five patients, including five with fluconazole-resistant urinary candidiasis, were included. Urine and plasma voriconazole concentrations, mean 1.7 mg/L (range: 0.3–12.6) and mean 2.0 mg/L (range: 0.1–11.1) respectively, exhibited a strong correlation (R2 = 0.88). None of the five patients treated for candidiasis experienced clinical or microbiological failure following treatment, with urine concentrations ranging from 0.5 to 2.7 mg/L. ConclusionsThe urinary diffusion of voriconazole resulted in drug exposure above the target minimum inhibitory concentration (MIC) in the five patients treated for voriconazole-susceptible Candida strains in urine. Therapeutic drug monitoring may allow optimize in situ concentrations.