Warfarin is an oral anticoagulant that requires individual monitoring since serious adverse events are common. CYP2C9 encodes for the enzyme mainly responsible of S‐warfarin’s metabolism. Polymorphisms in CYP2C9 have been previously found to be strongly associated with observed warfarin dose variability in different populations, but not in Caribbean Hispanics. Caribbean Hispanics originated as a result of a complex admixture among Caucasians, Africans and Amerindians ancestors‐a characteristic that should be considered for warfarin management. The rare loss‐of‐function CYP2C9*8 allelic variant is reportedly more prevalent among individuals with African heritage. Since Puerto Ricans has a significant contribution of African ancestry in their genetic backgrounds, this cross‐sectional study was aimed to determine the frequency of CYP2C9*8 in a cohort of 150 Puerto Rican patients undergoing warfarin therapy. DNA specimens were extracted and genotyped for the CYP2C9*8 using a PCR‐based Taqman genotyping assay. We found 3 heterozygous for the CYP2C9*8 variant in our study cohort, corresponding to a minor allele frequency of 1% (95%CI: 0.0026‐0.031). The observed frequency met Hardy‐Weinberg equilibrium. Allele frequency in our cohort was found to be significantly lower than that from a previous report in African‐Americans (0.01 versus 0.047, respectively, p=0.045 by two‐tailed z‐test), with a carrier frequency of 1 in 50 (Puerto Ricans) versus 1 in 11 (African‐Americans). Due to the CYP2C9*8 prevalence found among Puerto Ricans, we concluded that this variant should be included in any pharmacogenetic‐guided algorithm for warfarin dose predictions in this population. Approved by University of Puerto Rico, Medical Sciences Campus Institutional Review Board protocol A4070109. Grant Funding Source: Supported by NIH grants# 5SC2HL110393 (NHLBI) and grant# G12RR‐03051 (RCMI‐ NCRR).