The development of predictive modalities for musculoskeletal injuries in racehorses is a high priority for the international Thoroughbred industry to support racehorse welfare. Catastrophic fractures of the distal limbs are the most common cause of euthanasia in racing and are of particular concern. In humans, polygenic risk scores (PRS) derived from genetic risk variants for fracture can improve predictions from reliance on clinical risk factors alone. Injury data was accessed from The Jockey Club Equine Injury Database and 45K SNP genotypes were generated for >2000 Thoroughbred horses that raced in the US. These data were used to identify risk variants and develop and validate a PRS for fracture. Eleven lead SNPs in 13 genomic regions of interest significantly associated with fracture were included in the PRS. Using the PRS quartiles to stratify horses into risk groups identified 1.96 times greater risk of fracture in the highest risk group. Genetic screening of racehorses would enable targeting management resources to high risk horses that could reduce the incidence of fracture by up to 47.5%. The validity of the PRS is supported by the presence of genes in proximity to the risk variants with well-established roles in fracture and bone function. These results validate previously reported genomic regions associated with fracture in Thoroughbreds on chromosome 18, including the MSTN locus that is associated with speed variables and best race distance. Combining the PRS with other clinical/epidemiological risk factors will provide the greatest opportunity for management of individual horses for the prevention of fracture.