Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)

Inclusion Criteria: * Patients must have newly diagnosed MM confirmed by the presence of bone marrow plasmacytosis with \> 10 percent plasma cells, sheets of plasma cells, or biopsy-proven plasmacytoma. Patients must have Durie-Salmon Stage IIA-B or IIIA-B. Patients with non-secretory myeloma are eligible. (These patients will not be included in the analysis of response rates, but will be assessed for toxicity and survival). * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2, or 3 * ≥ 18 years of age. * Signed informed consent form * Expected survival of greater than 8 weeks * Capable of swallowing study medication tablets * Capable of following directions regarding taking study medication, or has a daily care provider who will be responsible for administering study medication. * Patients will be eligible for study even if they lack socioeconomic access to autologous transplantation. (These patients will be identified prior to randomization so as not to confound study results). * All patients (in the event that they are randomized to the thalidomide/dexamethasone arm) must agree to take part in the "System for Education and Prescribing Safety" (S.T.E.P.S.)™. They must sign a separate informed consent for this program. Exclusion Criteria: * Elevated direct bilirubin \> 2 mg/dl * Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) \> 2 times the upper limit of normal (ULN) * Absolute neutrophil count (ANC) \<1000/mL, unless felt to be secondary to myeloma * Ongoing radiation therapy, or radiation therapy within 3 weeks prior to first treatment, unless the acute side effects associated with such therapy are resolved. * Prior treatment for multiple myeloma * Prior bisphosphonate use is allowed but they must be discontinued before starting treatment. * Concurrent uncontrolled serious infection * Patients with peripheral (sensory) neuropathy, grade 3 or higher * Life-threatening illness (unrelated to tumor) * History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years. * Women of childbearing potential (unless utilizing birth control) or who are pregnant or nursing will be excluded from this study. * Patients with comorbid conditions that would contraindicate the use of vincristine, doxorubicin, dexamethasone, thalidomide, or zoledronate. * Plasma Cell Leukemia