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The aim of this study was to compare the efficacy and safety of posaconazole as invasive fungal infection prophylaxis in patients with hypoimmunity with other antifungals.A meta-analysis of randomized controlled trials (RCTs) identified in Pubmed, Embase and the Cochrane Library was performed.Four RCTs involving 1500 patients were included in this meta-analysis.Compared with other antifungals prophylaxis (fluconazole, itraconazole and amphotericin B lipid complex), posaconazole was superior for preventing invasive fungal infection demonstrated by the incidence rate (risk ratio [RR] =0.41, 95% confidence interval [CI] =0.27 to 0.64, P < 0.0001), and superior to fluconazole for preventing invasive aspergillosis infection (RR =0.23, 95% CI =0.11 to 0.47, P< 0.0001).The incidence of adverse events in posaconazole group was similar with other antifungal prophylaxis (RR=0.94, 95% CI =0.84 to 1.05, P=0.28).No significant difference was found in all-cause mortality rate between posaconazole and comparators (RR =0.82, 95% CI =0.65 to 1.03, P=0.08).When regarding the IFI-related mortality rate, posaconazole was significantly lower than comparators (RR =0.32, 95% CI =0.15 to 0.67, P =0.002).In conclusion,posaconazole is superior to fluconazole, intraconazole and ABLC as prophylaxis of invasive fungal infection, without increasing the adverse events.However, more RCTs are required to assess the efficacy and safety of posaconazole as IFI prophylaxis.