Only few studies have analyzed quality of life (QOL) and its association with prognosis in patients with multiple myeloma. We studied QOL at start of conventional treatment to evaluate the impact of symptomatic myeloma on QOL and to determine the prognostic significance of various dimensions of QOL. Our study provided further evidence of the significant impairment of QOL in patients with multiple myeloma at onset of therapy. Furthermore, our data showed a closer correlation between the more physical QOL scales such as pain, fatigue, physical functioning and global QOL with the activity of the disease than between psychosocial dimensions such as role, emotional, social, and cognitive functioning and the status of the disease. Multivariate analyses including each a QOL scale and known prognostic parameters (response to therapy, creatinine level, calcium, LDH, Hb, beta2-microglobulin, and albumin) revealed a marked difference in the prognostic significance between psychosocial and other QOL scales. All psychosocial dimensions of QOL were found to be independent prognostic factors, while physical QOL and global QOL were eliminated by disease-associated prognosticators. Taken together, QOL was found to be significantly impaired in myeloma patients at start of therapy. Psychosocial, but not physical dimensions of QOL were found to be independent prognostic factors.