Infections are the primary cause of morbidity and mortality in multiple myeloma (MM) patients (pts). The aim of our retrospective analysis was to evaluate incidence and course of COVID-19 infection in a cohort of 351 MM outpatients treated with novel drugs. COVID-19 disease was detected in 50/351 pts (14%); median age was 68 years. Gender, ISS stage, and last treatment lines were as follows: male 32, female 18; ISS-I 19, ISS-II 20, ISS-III 11; daratumumab-based 15, lenalidomide-based 12, bortezomib-based 17, other 6. Positive PCR test at COVID-19 diagnosis was present in all pts; anti-myeloma treatment was interrupted. Hospitalizations for COVID-19 pneumonia were necessary for 28/50 pts (56%), 18/50 pts (36%) in standard unit (SU) 10/50 pts (20%) in intensive care unit (ICU), and 9/50 pts (18%) died. The statistically significant parameters for COVID-19 hospitalization were as follows: responsive versus non-responsive disease (p = 0.027), ECOG performance status 0-2 versus >= 3 (p = 0.014), presence of comorbidities (0-1 versus >= 2, p = 0.043). The statistically significant factors for COVID-19 death were as follows: ECOG 0-2 versus >= 3 (p = 0.001), presence of comorbidities (0-1 versus >= 2, p = 0.007), serious course of COVID-19 disease with ICU hospitalization (SU versus ICU, p = 0.001). None of the other studied risk factors was associated with poor outcome (age, gender, ISS stage, immunoparesis, type of anti-myeloma treatment). Full recovery from COVID-19 infection was observed in 41/50 pts (82%) in median of 32 days. The course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths.