High-dose melphalan and autologous hematopoietic stem cell transplantation (HSCT) is a standard treatment for myeloma, but very little is known about the psychosocial or quality-of-life difficulties that these patients encounter during treatment. Data regarding older patients is particularly scarce. Using a prospective design, this investigation evaluated 94 patients at stem cell collection and again after high-dose therapy and transplantation. Outcomes included quality-of-life (FACT-BMT) and psychosocial adjustment (ie, Brief Symptom Inventory, Impact of Events Scale, and Satisfaction with Life Scale). Findings were compared with age- and sex-adjusted population norms and with transplantation patient norms. At stem cell collection, physical deficits were common, with most patients scoring 1 standard deviation below population norms for physical well-being (70.2%) and functional well-being (57.5%), and many reporting at least moderate fatigue (94.7%) and pain (39.4%). Clinically meaningful levels of anxiety (39.4%), depression (40.4%), and cancer-related distress (37.0%) were evident in a notable proportion of patients. After transplantation, there was a worsening of transplant-related concerns (P < .05), depression (P < .05), and life-satisfaction (P < .001); however, pain improved (P < .01), and social functioning was well preserved. Overall, the declines in functioning after transplantation were less pronounced than anticipated. Older patients were not more compromised than younger ones; in multivariate analyses, they reported better overall quality of life (P < .01) and less depression (P < .05) before transplantation. Our findings emphasize the importance of early screening and intervention.