Noninfectious pulmonary dysfunction (NIPD) is a common and often fatal complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). An insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene has been extensively studied in relation to cardiovascular and renal disease, and lung fibrosis. In pulmonary fibrosis, D-allele frequency is significantly higher than in the control population. We hypothesized that a similar mechanism exists between post-HSCT NIPD and pulmonary fibrosis in the absence of HSCT. We retrospectively analyzed the incidence of NIPD and the ACE genotype polymorphism in 118 Japanese patients who underwent HSCT from HLA-identical sibling donors. NIPD occurred in 17 cases. Deletion/deletion genotype carriers were more common in the NIPD group than in the other 101 patients (41.2 vs 11.9%; hazard ratio, 5.19; 95% confidence interval, 1.67-16.21). There were no significant relationships between the clinical characteristics of patients and the development of NIPD. These findings suggest that the ACE genotype is associated with the development of NIPD following HSCT. This study is the first to report the relationship between genetic background and NIPD.