SW033291 is a potent and selective 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme inhibitor. 15-PGDH is a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. SW033291 also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.