Objective: Analyze the effectiveness of four therapeutic programs in patients with Multiple Myeloma (MM), seen in the last 20 years in a single hospital. Patients and Methods: Retrospective and comparative. With symptomatic MM patients de novo, treated from January-1995to December-2014. Characteristics of the MM and the impact to organs were studied. Treatment: melphalan-prednisone (MM01), polichemotherapy-interferon (MM02), melphalan-prednisone-thalidomide (MM03) and bortezomib-cyclophosphamide (or doxorubicin) - dexamethasone (MM04). Results: 237 patients. No difference in gender. Age: median 58 years; mode 50. No-secretory: 25%; Type G 54%; kappa chains 91%; plasmoblastss 26% (average); plasmacytomes in 23%. With 27% of kidney failure; hyperviscosity 4%.Without predominance in any therapeutic arm (p> 0.09). Distribution of treatments: MM01 39 (17%); MM0263 (27%); MM03 85 (37%); MM04 44 (19%); 6 eliminated by early death (3%). Remissions (complete or partial): MM01 87%; MM02 73%; MM03 92%; MM04 85%. The average of (PFS) progression-free survival (months): MM01 24; MM02 38; 86 MM03; MM04 63. 81 patients received another treatment, by failure or progression. Variables with negative prognostic value (p< 0.03): Salmon-Durie, ISS, existence of plasmacytoms, hypoalbuminemia, and amount of plasmoblasts. Conclusion: The age of presentation is unusually low. The PFS is comparable to other studies. The scale of Salmon-Durie is as useful as the ISS.