Objective To assess the efficacy and safety of posaconazole for prophylaxis of invasive fungal infections.Methods Databases such as PUBMED,Medline,Embase,Cochrane Library,SinoMed,CNKI,VIP Information and conference proceedings were searched for relevant randomized controlled trials (RCTs) about posaconazole for prophylaxis of invasive fungal infections.The cut-off time is December 2014.And reference of the included articles were also manually searched.Quality of included studies were assessed and data of which were extracted.Both Review Manager 5.2 and Stata 12.0 software were used.Results Four RCTs which included 1 476 patients met the search criteria were assessed.Meta analysis results:the IFI rate[RR=0.41,95%CI (0.27,0.63),P<0.000 01],especially in prophylaxis for invasive aspergillosis (posaconazole group significantly reduced:the IFI rate,especially in prophylaxis for invasive aspergillosis (posaconazole vs fluconazole,P<0.000 1);and mortality from IFI.However,no significant differences were observed in adverse reactions,therapy discontinued because of adverse reactions,all-cause mortality rate between posaconazole and controlled groups (P>0.05).For subgroup analysis,there was no significant difference in both the rates of adverse reactions and invasive candidiasis infection between posaconazole and fluconazole (P>0.05).Conclusion Posaconazole can be used as a good alternative of amphotericin B lipid complex,fluconazole or itraconazole for prophylaxis of invasive fungal infections.Posaconazole significantly improves the effect of prophylaxis and decreases IFI associated mortality but with no risk of increase in adverse events.