This prospective multicentre study evaluates the utility of the haematopoietic cell transplantation (HCT) Frailty Scale in 269 adults with multiple myeloma (MM) undergoing autologous haematopoietic cell transplantation (auto-HCT). Frailty was assessed in all patients at the first consultation, at transplant admission and on day +100. Quality of life (QoL) was measured using the EuroQol (EQ-5D-5L) questionnaire. At the first consultation, 23.8% were fit, 57.6% pre-frail and 18.6% frail. Frailty was associated with advanced disease stage, reduced Karnofsky Performance Status and older age. At HCT admission, 32.3% of patients showed changes in frailty status, confirming its dynamic nature. Frail patients had higher readmission rates (14.7%) and significantly lower QoL (p < 0.001) compared to others. Although differences in non-relapsed mortality (NRM) were not statistically significant, frail and pre-frail patients showed higher 1-year NRM (4.8% and 3.4%) compared to fit patients (0%). By day +100, 33.6% were fit, 55.9% pre-frail and 8.2% frail, with frail patients continuing to report poorer QoL. In conclusion, the HCT Frailty Scale is a valuable tool for identifying and monitoring frailty in MM patients undergoing auto-HCT. As frailty status evolves over time, ongoing assessment is essential to guide personalized care, reduce complications and improve outcomes and QoL.