Mismatch for the adhesion molecule CD31 (PECAM-1) has been associated in some studies with graft-versus-host disease (GVHD), suggesting a role for CD31 as a minor histocompatibility antigen. We examined polymorphisms of the CD31 (PECAM-1) gene in 74 patients and their human leukocyte antigen-matched sibling donors, comparing CD31 genotype with outcomes of occurrence of GVHD and survival using regression analysis. Polymorphisms in codon 125, 563, and 670 are strongly linked forming conserved haplotypes. Donor CD31 (val/asn/gly) haplotype was associated with acute GVHD (P=0.004, odds ratio 7.5). In addition, donor heterozygosity at codon 563 was significantly associated with worse overall survival after correcting for other known variables by regression modeling. Peptide binding predictions support the hypothesis that CD31 could act as a minor histocompatibility antigen. Assessment for CD31 gene status may be of value in pretransplant assessment of bone marrow transplant recipients and donors for prediction of likely transplant-related complications.