Background: Frailty is a state characterized by diminished physiological reserve and increased vulnerability to stress, and adversely affects outcomes in older patients with cancer. Geriatric assessments are not routinely used to screen older HCT (hematopoietic cell transplant) recipients. There is limited knowledge of the impact of pre-HCT frailty on severe/ life-threatening (CTCAE, version 5.0) grade 3-4 non-hematologic toxicities within 1y after HCT. We aimed to determine the relationship between pre-HCT frailty and grade 3-4 non-hematologic toxicities and mortality in HCT recipients, and also examined whether age at HCT moderated that association. Methods: In a prospective longitudinal study of 117 patients undergoing HCT at age ≥ 40y, we performed pre-HCT geriatric assessments. Frailty was assessed using Fried’s criteria. Post-HCT toxicities were abstracted through chart reviews Results: Median age at HCT was 60y (40-73). Pre-HCT frailty could be evaluated in 98 (84%) patients [(51 autologous, 47 allogeneic (allo)]. Pre-HCT comorbidity index (CI) was high in 27%, intermediate in 40% and low in 33%. The prevalence of pre-HCT frailty was 21%. Overall, frail recipients (vs. non-frail) had a higher cumulative incidence of any grade 3-4 toxicity [86% (95% CI: 62-100%) vs. 70% (57-83%), p = 0.03]; and the following organ specific grade 3-4 toxicities: non-neutropenic infections [(38% (17-59%) vs. 13% (6-20%), p < 0.01)]; nervous system disorders [(19% (3-35%) vs. 4% (0-8%), p = 0.02)]; and pneumonia [(38% (17-59%) vs. 10% (4-17%), p < 0.01]. Frail recipients also had a higher overall mortality [52%, (30-75%) vs. 19%, (11-28%) (p < 0.01)]. In Cox regression analysis controlling for age, donor type, disease risk, conditioning and HCT-CI, frail recipients were 1.9 fold more likely to suffer any grade 3-4 toxicities (p = 0.03), 4-fold more likely to suffer non-neutropenic infections and pneumonia, both p = 0.01; and 8.6-fold more likely to suffer nervous system disorders, p = 0.01. Frail recipients who underwent an allo-HCT were at 2.7 fold higher risk of death vs. non-frail allo- HCT recipients, p = 0.06. Conclusions: The higher toxicity and mortality in frail recipients needs attention. Studies focusing on pre-HCT interventions to reduce frailty are needed.