Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. TheIkarostranscription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized thatIkarosmight influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relativeIkarosexpression. Patients were divided into two groups, according toIkarosexpression in the graft and in the recipients’ PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used forIkarosexpression in the graft, and a cutoff of 0.79 was used forIkarosexpression in the recipients’ PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16–80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10–43 months). There was no association betweenIkarosexpression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. HigherIkarosexpression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higherIkarosexpression in the recipients’ PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion,Ikarosexpression in the graft and in the recipients’ PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD.Ikarosexpression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.