Multiple myeloma (MM) is a disease of aging adults and autologous stem cell transplant (ASCT) is considered the standard of care. As the population ages a growing number of older adults will undergo ASCT and an objective approach to estimate physiologic reserve and transplant morbidity risk is warranted. Here, we evaluate assess p16INK4a (p16), a molecular aging biomarker, along with geriatric metrics to determine risk of transplant toxicity. Methods: We prospectively evaluated 100 MM patients for frailty before and after ASCT using a Geriatric Assessment (GA) and collected T-cells for analysis of p16 using a custom nanostring codeset. Results: Pre-transplant physical function was predicative of hospital length of stay (LOS). Each one-unit increase in physical function score, the average LOS decreased by 0.52 days (95% CI, −1.03–0.02); p = .04). Similarly, higher self-report of ADL/IADL (Human Activity Profile was associated with shorter LOS (0.65 less days (95% CI −1.15 to −0.15), p = .01). Patients with anxiety/depression (OR = 1.10 (95% CI 1.00–1.22), p = .056), lower handgrip strength (OR = 0.90 (95% CI 0.82–0.98), p = .02), falls (OR = 1.60 (95% CI 1.07–2.38), p = .02), or weight loss (OR = 5.65 (95% CI 1.17–25.24), p = .03) were more likely to be re-admitted. The estimated EFS at 1-year was 85% (95% CI, 75–91) with median follow-up of 15.7 months. Weight loss was a significant predictor of EFS (HR = 3.13 (95% CI 1.15–8.50), p = .03). Frailty assessment by self-reported fatigue minimally correlated with T-cell p16 expression (r = 0.28; p = .02). Age, Karnofsky Performance Status (KPS), or Hematopoietic cell transplantation-specific Co-Morbidity Index (HCT-CI) did not predict hospital LOS or readmissions. Conclusions: Our data illustrate that a GA can identify individuals with MM who are at greater risk for morbidity following ASCT.