The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma (MM). Although the initial response rates and toxicity are well known, long-term outcome is not well described. We studied 286 consecutive patients with newly diagnosed MM initially treated with Len-Dex. The median (range) age at diagnosis was 63 (28-92) years, 166 (58%) patients ≤ 65 years and 175 (61%) male. The median estimated duration on Len-Dex was 5.3 months with overall response (≥ partial response) of 72%, including 26% with very good partial response or better. The median overall survival (OS) from the diagnosis was not reached (NR) and the estimated 5-year survival was 71%. The median time to first disease progression, irrespective of transplant status, was 30.2 months. Overall, 143 (50%) patients underwent stem cell transplant. The median OS was NR for patients ≤ 70 years and 5.8 years for the older patients (P=0.01). The 5-year OS estimate for patients in International Staging System stage 1, 2 and 3 were 82, 65, and 44% respectively. There were 21 new second malignancies after MM diagnosis (6.6%). The median survival exceeding 7 years reflects the efficacy of novel agents. The risk of second malignancies doesn't appear to be excessive in this population.