Graft failure (GF) after hematopoietic cell transplant (HCT) occurs in 5-30% of patients. GF can be accompanied by neutropenia (NGF) or can result with adequate neutrophils, but loss of donor chimerism (non-neutropenic graft failure, NNGF). In this report, we describe the outcomes of 95 patients treated with a second HCT for GF at the University of Minnesota; 62 with NGF and 33 with NNGF. The cumulative incidence of neutrophil recovery at 42 days after second HCT was 45% for NGF and 88% for NNGF. A second GF occurred in 34 NGF (55%) and in 9 NNGF (27%) patients. The incidence of Grade III-IV acute graft versus host disease (GVHD) was 8% (95% confidence interval (CI), 1-16%) and 12% (95% CI, 1-23%) for NGF and NNGF, respectively. From the 2nd HCT, 1-year overall survival (OS) was 44% (95% CI, 34-54%), [NNGF: 76% (95% CI, 57-87%) and NGF: 27% (95% CI, 17-39%)]. The most common cause of death after second HCT was infection (52%). In summary, the outcomes of second HCT after NGF and NNGF are different with much worse outcomes for NGF necessitating new approaches for this complication.