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Newer chemotherapeutic protocols as well as high-dose chemotherapy have increased the response rate in myeloma. However, these treatments are not curative. Effective maintenance strategies are now required to prolong the duration of response. We conducted a randomized trial of maintenance treatment with thalidomide and pamidronate. Two months after high-dose therapy, 597 patients younger than age 65 years were randomly assigned to receive no maintenance (arm A), pamidronate (arm B), or pamidronate plus thalidomide (arm C). A complete or very good partial response was achieved by 55% of patients in arm A, 57% in arm B, and 67% in arm C (P= .03). The 3-year postrandomization probability of event-free survival was 36% in arm A, 37% in arm B, and 52% in arm C (P< .009). The 4-year postdiagnosis probability of survival was 77% in arm A, 74% in arm B, and 87% in arm C (P< .04). The proportion of patients who had skeletal events was 24% in arm A, 21% in arm B, and 18% in arm C (P= .4). Thalidomide is an effective maintenance therapy in patients with multiple myeloma. Maintenance treatment with pamidronate does not decrease the incidence of bone events.