With the availability of novel agents, the overall survival (OS) in patients diagnosed with multiple myeloma (MM) has improved over the last decade. Data on 40,294 MM patients in the years from 1973 to 2003 were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute. Statistical analyses evaluating gender, race, age, and year of diagnosis were performed using univariate and multivariate Cox regression models for the OS endpoint. The mean patient age at diagnosis was 68.3 years. Mean survival was 30 months (median = 19 months). Asian/Pacific Islander race was associated with an improved OS, HR 0.90 (CI 0.86-0.95, P < 0.001). American Indian/Alaska Native race was associated with a decreased OS, HR 1.18 (CI 1.01-1.38, P = 0.040). Multivariate analysis did not reveal statistically significant differences in OS between patients in the white and black race (P = 0.709). Younger age (age <65, and 65-75) was associated with improved OS when compared with patients >75 years of age (all P < 0.001). Recent treatment decades (1983-1992 and 1993-2003) were associated with improved OS on multivariate analysis with HR 0.88 (CI 0.88-0.89, P < 0.001) and HR 0.83 (CI 0.81-0.85, P < 0.001), respectively. As the largest population analysis to date, this study reveals a statistically significant improvement in OS for patients who were treated in more recent decades, even before the availability of novel agents. Patients who were <65 years of age and Asian/Pacific Islander race groups exhibited superior levels of OS, whereas American Indian/Alaska Native groups had decreased OS.