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To assess the usefulness of the “Candida score” (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point.Prospective, cohort, observational study.Thirty-six medical-surgical intensive care units of Spain, Argentina, and France.A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007.Clinical data, surveillance cultures for fungal growth, and serum levels of (1–3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition ×1, plus surgery ×1, plus multifocal Candida colonization ×1, plus severe sepsis ×2. A CS ≥3 accurately selected patients at high risk for IC. The colonization index was registered if ≥0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06–3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p ≤ 0.001). The area under the receiver operating characteristic curve for CS was 0.774 (95% CI 0.715–0.832) compared with 0.633 (95% CI 0.557–0.709) for CI. (1–3)-Beta-d-glucan was also an independent predictor of IC (odds ratio 1.004, 95% CI 1.0–1.007). The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81–12.45).In this cohort of colonized patients staying >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.