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The use of antifungal prophylaxis remains controversial in most populations including surgical intensive care unit patients. A meta-analysis of randomized controlled trials was performed to evaluate the safety and effectiveness of azoles as antifungal prophylaxis in high-risk patients receiving treatment in the surgical intensive care unit.Data were obtained from PubMed, Current Contents, Cochrane central register of controlled trials, and references from relevant articles.Randomized controlled trials using azoles as antifungal prophylaxis vs. placebo were included in the study.Two independent reviewers extracted data concerning the development of fungal infections (superficial or invasive), adverse effects, and mortality.Six randomized controlled trials were included in the main analysis. Publication bias and statistically significant heterogeneity were not observed among the analyzed studies. Patients receiving antifungal prophylaxis developed fewer episodes of candidemia (odds ratio [OR] = 0.28, 95% confidence interval [CI] 0.09–0.86), nonbloodstream invasive fungal infections (OR = 0.26, 95% CI 0.12–0.53), and noninvasive (superficial) fungal infections (OR = 0.22, 95% CI 0.11–0.43), respectively. No reduction in mortality was observed among patients who received azole prophylaxis (OR = 0.74, 95% CI 0.52–1.05). There was no significant difference in reported adverse effects (OR = 1.28, 95% CI 0.82–1.98).Despite its limitations, our meta-analysis suggests that the prophylactic use of azoles in high-risk surgical intensive care unit patients is associated with a reduction of fungal infections but not in all-cause mortality. However, although not noted in the analyzed randomized controlled trials, there is concern about the use of azoles due to possible shift toward non-albicans species and development of resistance to azoles.