OBJECTIVES: Invasive  Fungal  Infections  (IFIs)  present  a  major  issue  in  clinical  practice,  due  to  their  high  morbidity  and  mortality  rates.  In  a  pivotal  multicentre,  randomized  clinical  trial  posaconazole  prophylaxis  prevented  IFIs  more  effectively  than  did  either  fluconazole  or  itraconazole,  and  improved  overall  survival.  The  aim  of  this  study  was  to  perform  an  economic  evaluation  of  the  afore-mentioned  therapeutic  strategies  for  IFI  prophylaxis  in  neutropenic  patients,  in  the  Greek  healthcare  setting.  METHODS: A  decision  analytic  model  was  developed,  which  described  the  course  of  neutropenic  patients  under  posaconazole  or  standard  azole  (fluconazole  or  itraconazole)  treatment.  The  effectiveness  data  for  each  treatment  regimen  were  derived  from  published  results  of  a  pivotal,  multicentre,  randomized  clinical  trial.  The  cost  and  healthcare  resources  utilization  data  used,  depict  Greek  clinical  practice  and  are  derived  from  official  Greek  sources.  In order to obtain some of the model imputs,  expert  opinion  from  Greek  Hematologists  specializing  in  treating  IFIs,  was  also used. RESULTS: Prophylaxis  with  Posaconazole  resulted  in  fewer  IFIs  (0,05  vs.  0,11  per  patient)  compared  to  treatment  with  fluconazole  or  itraconazole,  during  the  first  100  days  from  initiation  of  prophylaxis  treatment.  The  cost  per  avoided  IFI  with  Posaconazole  was  6,455€,  while  the  cost  for  every  incremental  life  year  gained  (LYG)  was  estimated  at  24,196€.  Extensive sensitivity analyses (one-way and probabilistic) corroborated the base-case results. CONCLUSIONS: :  The  utilization  of  Posaconazole  for  prophylaxis  of  IFIs  in  hematology  patients  with  neutropenia  is  a  therapeutic  strategy  that provides  superior  clinical  efficacy,  while  being  cost-effective  compared  to  alternative  therapies.