Allogeneic stem cell transplantation (alloSCT) is a highly effective immunotherapy for haematologic malignancies. However infection, acute organ dysfunction and graft versus host disease (GVHD) impact negatively on patient outcomes. Pre-transplant conditioning regimes are associated with high levels of immunogenic cell death and the release of extracellular ATP which binds to the P2X7 receptor. Signalling through the P2X7 receptor may lead to activation of downstream effectors that influence alloSCT outcome. In this study we examined the effect of gain and loss of function P2X7 SNPs in 333 alloSCT recipients and correlated to acute GVHD, chronic GVHD, relapse free survival and overall survival. Inheritance of loss of function SNPs (Arg307Gln or Glu496Ala) was associated with reduced rates of aGVHD while Ile568Asn was associated with increased aGVHD reflecting the the differential effects of these SNPs on P2X7 function. No one single SNP was associated with changes in relapse free or overall survival. However patients with the major gain of function variant haplotype (homozygous Gln460Arg- Ala348Thr) had significantly reduced relapse free and overall survival compared to other patients. Our findings demonstrate that recipient immunology has a significant impact on alloSCT outcome and with validation, analysis of P2X7 SNPs could be added to alloSCT risk stratification models.