Peripheral nerves promote mouse bone marrow regeneration by activating b2 and b3 adrenergic receptor signaling, raising the possibility that non-selective b blockers could inhibit engraftment after hematopoietic cell transplants (HCTs). We observed no effect of b blockers on steady-state mouse hematopoiesis. However, mice treated with a non-selective b blocker (carvedilol), but not a b1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs. At two institutions, patients who received non-selective, but not b1-selective, b blockers after allogeneic HCT exhibited delayed platelet engraftment and reduced survival. This was particularly observed in patients who received post-transplant chemotherapy for graft-versus-host disease prophylaxis, which also accentuated the inhibitory effect of carvedilol on engraftment in mice. In patients who received autologous HCTs, non-selective b blockers were associated with little or no delay in engraftment. The inhibitory effect of non-selective b blockers after allogeneic HCT was overcome by transplanting larger doses of hematopoietic cells.