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Background: This retrospective one-center study demonstrates the complications related to high-dose therapy with autologous stem cell support (HDT) and the survival of multiple myeloma (MM) patients according to age groups. Methods : We categorized the patients into two groups: those who were ≤65 years old (group 1) ( N = 115) and those who were >65 years old (group 2) ( N = 26). The mean duration of follow-up was 48 (1-125) months. Results: In group 2 patients, the use of a reduced dosage of melphalan (12 [46%] versus 30 [26%]) was more frequent in comparison to group 1 ( p = 0.046). There was a statistically significant difference between the two groups regarding the neutrophil engraftment days ( p = 0.001) and the median progression-free survival (PFS) ( p = 0.02). The PFS was 44 months for group 1 and 30 months for group 2. There was no statistically significant difference between the groups in relation to the median duration of hospitalization, presence of bacteremia, intravenous antibiotic administration, and overall survival (OS). Conclusions: The study's results indicate that HDT is a reliable method of treatment for older patients with MM, provided that they obtain a suitable conditioning regimen and, furthermore, these patients achieved a comparable OS rate to that of younger patients.