Background: Cy is the backbone for many SCT conditioning regimens and is used post-SCT to prevent graft vs. host disease (GVHD). It has been proposed that genetic polymorphisms impact Cy exposure and clinical outcomes; however, no PGx studies have been performed in pts receiving FluCyTBI-postCy. Methods: Germline DNA from SCT pts receiving FluCyTBI-postCy was genotyped using a custom Ion AmpliSeq™ PGx Panel for polymorphisms in: ALDH1A1 (*2), ALDH3A1 (Pro329Ala), GSTA1 (135T > C), GSTM1 (null), GSTP1 (Ile105Val, Ala114Val), CYP2B6 (*2, *4, *5, *6, *18, *22), CYP2C8 (*2, *3), CYP2C9 (*2, *3, *8, *11), CYP2C19 (*2, *3, *17), CYP3A4 (*1B, *22), and CYP3A5 (*3, *6, *7). Phenotypes (poor [PM], intermediate [IM], normal [NM], and rapid metabolizers [RM]) were inferred based on literature. Cy 14.5 mg/kg IV was given on days -6 & -5 pre-SCT, and 50 mg/kg on days +3 & +4 post-SCT. Univariate logistic regression was used to investigate the association between polymorphisms and any grade cardiotoxicity, hemorrhage cystitis [HC], liver toxicity, and/or acute GVHD up to day +100. Univariate Cox proportional hazards regression was used to investigate the association between polymorphisms and overall [OS] & progression-free survival [PFS]. Results: In 59 evaluable pts, the median age was 57 (24-77), 61% were male, 73% received haploidentical SCT and 27% matched related donor SCT. The table summarizes significant findings (P < 0.05). Conclusions: Several genes involved in the activation (CYPs) and inactivation (ALDHs&GSTs) of Cy and its metabolites were associated with SCT outcomes and toxicities. Prospective studies exploring the combined effects of these genes on outcomes are needed to validate findings.